Full list of Cell-Penetrating Peptides

Table 1 Selection of cell-penetrating peptides

(Reference: https://doi.org/10.1007/978-981-13-8747-0, Ülo Langel, CPP, Cell-Penetrating Peptides, 2019)

Name Sequence
2 DSLKSYWYLQKFSWR (Kondo et al. 2012)
18A DWLKAFYDKVAEKLKEAF (Datta et al. 2000)
α1H KSKTEYYNAWAVWERNAP (Gomarasca et al. 2017)
α2H GNGEQREMAVSRLRDCLDRQA (Gomarasca et al. 2017)
A22p HTPGNSNKWKHLQENKKGRPRR (Shin et al. 2014)
Ac-18A-NH2 DWLKAFYDKVAEKLKEAF) (Wimley and White 2000)
aCPP Typical sequence R9GPLGLAGE8 (Li et al 2015)
AdVpVI(33-55) Ac-GAFSWGSLWSGIKNFGSTVKNYG (Murayama et al. 2016)
AIP6 RLRWR (Wang et al. 2011)
all-d DsC18 Glrkrlrkfrnkikek (Bergmann et al. 2017)
αgliadin(31-43) LGQQQPFPPQQPY (Paolella et al. 2018)
Alyteserin-2a ILGKLLSTAAGLLSNL (Conlon et al. 2013)
ANG TFFYGGSRGKRNNFKTEEY (Demeule et al. 2008)
ApoE(141–150) Ac-LRKLRKRLLRX-Bpg-G (Shabanpoor et al. 2017)
ApoE-derived Ac-LRKLRKRLLR (Tailhades et al. 2017)
Arf(1-22) MVRRFLVTLRIRRACGPPRVRV (Johansson et al. 2008)
AT1002 FCIGRL (Gopalakrishnan et al. 2009)
AT1AR(304-318) FLGKKFKKYFLQLLK (Östlund et al. 2005)
Bac7 RRIRPRPPRLPRPRPRPLPFPRPGPRPIPRPL (Sadler et al. 2002)
BGPC7-FHV RRRRNRTRRNRRRVR-RRFYGPV (Wongso et al. 2017)
Bim EIWIAQELRRIGDEFNAYYARLLC (Kim et al. 2017)
BP16 KKLFKKILKKL (Soler et al. 2014)
BP100 KKLFKKILKYL (Eggenberger et al. 2009)
BPP13a GGWPRPGPEIPP (Sciani et al. 2017)
bPrPp(1-30) MVKSKIGSWILVLFVAMWSDVGLCKKRPKP (Magzoub et al. 2006)
BR2 RAGLQFPVGRLLRRLLR (Lim et al. 2013)
Buforin II TRSSRAGLQFPVGRVIIRLLRK (Park et al.1998)
Buforin IIb RAGLQFPVG[RLLR]3 (Lee et al. 2008)
C6M1 RLWRLLWRLWRRLWRLLR (Jafari et al. 2014)
C105Y CSIPPEVKFNKPFVYLI (Rhee and Davis 2006)
CADY GLWRALWRLLRSLWRLLWRA cycteamide (Crombez et al. 2009a)
CAR CARSKNKDC (Toba et al. 2014)
CA-Tat KWKLFKKYGRKKRRQRRR (Lv et al. 2017)
CB5005 M KLKLALALALA (Zhang et al. 2016)
CDB3 REDEDEIEW (Issaeva et al. 2003)
CendR RPARPAR (Hu et al. 2014)
cF<tR4 cyclic F<tRRRRQ (Qian et al. 2014)
CGKRK CGKRK (Griffin et al. 2017)
CIGB-300 cyclic CWMSPRHLGTC-Tat (Perera et al. 2012)
CIGB-552 Ac-HARIKpTFRRlKWKYKGKFW (Fernandez Masso et al. 2013)
CLIP6 KVRVRVRVpPTRVRERVK (Soudah et al. 2017)
CooP ACGLSGLGVA (Hyvonen et al. 2014)
CpMTP ARLLWLLRGLTLGTAPRRA (Jain and Chugh 2016)
CPNT STSGTGKMTRAQRRAAARRNRA (Qi et al. 2011)
CPP1 (KFF)3K (Patel et al. 2017)
CPP33 RLWMRWYSPRTRAYG (Lin et al. 2018)
CPP-C PIEVCMYREP (Nakayama et al. 2011)
CPPecp NYRWRCKNQN (Fu et al. 2017)
C-peptide GPGLWERQAREHSERKKRRRESECKAA (Fan et al. 2016)
CRGDK CRGDK (Zhao et al. 2018)
Crotamine YKQCHKKGGHCFPKEKICLPPSSDFGKMDCRWRWKCCKKGSG (Rodrigues et al. 2012)
cSN50 AAVALLPAVLLALLAPVQRKRQKLMP (Torgerson et al. 1998)
65-2CTS CPYVNQRPQKARYRNG (Percipalle et al. 2003)
CWR8K CWR8K (Sasaki et al. 2008)
CyLoP-1 CRWRWKCCKK (Ponnappan et al. 2017)
Cyt c(77–101) GTKMIFVGIKKKEERADLIKKA (Howl and Jones 2015)
DAG cyclic CDAGRKQKC (Mann et al. 2017)
D-JNKI-1 RPKRPTTLNLFPQVPRSQDT (Bonny et al. 2001)
DK17 DRQIKIWFQNRRMKWKK (Bera et al. 2016)
DLP ACKTGSHNQCG (Kumar et al. 2015)
DMBT1-derived GRVEVLYRGSW and GRVRVLYRGSW (Tuttolomondo et al. 2017)
dNP2 KIKKVKKKGRK-KIKKVKKKGRK (Lim et al. 2015)
DPV3 RKKRRRESRKKRRRES (Tacken et al. 2008)
DPV1047 CVKRGLKLRHVRPRVTRMDV (De Coupade et al. 2005)
DRTTLTN DRTTLTN (Gennari et al. 2016)
DS4.3 RIMRILRILKLAR (Jeong et al. 2014)
Dynorphin A YGGFLRRIRPKLKWDNQ (Marinova et al. 2005)
EA GLKKLAELAHKLLKLGC (Yang et al. 2014)
EB1 LIRLWSHLIHIWFQNRRLKWKKK (Lundberg et al. 2007)
EF GLKKLAELFHKLLKLGC (Yang et al. 2014)
EHB RCSHYTGIRCSHMAATTAGIYTGIRCQHVVL-C6H (Cao et al. 2018)
EPRNEEK EPRNEEK (Orihuela et al. 2009)
F3** diphosphorylated dipeptide (Miao et al. 2016)
G4R9L4 G4R9L4 (Ramakrishna et al. 2014)
GALA WEAALAEALAEALAEHLAEALAEALEALAA (Li et al. 2004)
GeT KIAKLKAKIQKLKQKIAKLK (Rakowska et al. 2014)
gH625 HGLASTLTRWAHYNALIRAF (Galdiero et al. 2015)
Gi3α(346-355) KNNLKECGLY (Jones et al. 2005)
Glu-Lys EEEAAKKK (Lewis et al. 2010)
GV1001 EARPALLTSRLRFIPK (Kim et al. 2016a)
GWH1 GYNYAKKLANLAKKFANALW (Serna et al. 2017)
H2A derived SGRGKQGGKARAKAKTRSSRAGLQFPVGRVHRLLRKG (Rosenbluh et al. 2004)
H6R6 H6R6 (Sun et al. 2017)
H16 H16 (Iwasaki et al. 2015)
HA2(1-23) GLFGAIAGFIENGWEGMIDGWYG (Esbjörner et al. 2007)
HAIYPRH HAIYPRH (Shteinfer-Kuzmine et al. 2017)
hBD3-3 GKCSTRGRKCCRRKK (Lee et al. 2015b)
HBP GKRKKKGKGLGKKRDPCLRKYK (Luo et al. 2016)
hLF KCFQWQRNMRKVRGPPVSCIKR (Duchardt et al. 2009)
Hph-1 YARVRRRGPRR (Jung et al. 2011)
HR9 CH5-R9-H5C (Liu et al. 2013a)
Hst5 DSHAKRHHGYKRKFHEKHHSHRGY (Luque-Ortega et al. 2008)
I1WL5W WKKIWSKIKKLLK (Bi et al. 2014)
I4WL5W IKKWWSKIKKLLK (Bi et al. 2014)
ID No.2 MAAWMRSLFSPLKKLWIRMH (Eudes and Macmillan 2014)
IMT-P8 RRWRRWNRFNRRRCR (Gautam et al. 2016)
INF GLFEAIEGFIENGWEGMIDGWYGC (Pichon et al. 1997)
iNGR CRNGRGPDC (Alberici et al. 2013)
isl-1 RVIRVWFQNKRCKDKK (Kilk et al. 2001)
JB9 cskc (Basu and Wickstrom, 1997)
JB434 R9GGLAA-Aib-SGWKH6 (Sangtani et al. 2018)
KAFAK KAFAKLAARLYRKALARQLGVAA (Bartlett et al. 2013)
KALA WEAKLAKALAKALAKHLAKALAKALKACEA (Wyman et al. 1997)
Kalata B1 polycyclic CGETCVGGTCNTPGCTCSWPVCTRNGLPV (Daly et al. 1999)
(KFF)3K (KFF)3K (Rownicki et al. 2017)
K-FGF AAVLLPVLLAAP (Lin et al. 1995)
KH (KH)9 (Chuah et al. 2016)
KLA KLAKLAKKLAKLAK (Huang et al. 2017)
KLAK KLALKLALKALKAALKLA (Oehlke et al. 1998)
KLA-R7 KLAKLAKKLAKLAKGGRRRRRRR (Lemeshko, 2013)
KP MAPTKRKGSCPGAAPNKKP (Villa-Cedillo et al. 2017)
KST peptide STGKANKITITNDKGRLSK (Adachi et al. 2017)
L1−6 PLILLRLLR (Schmidt et al. 2017)
L5a RRWQW (Liu et al. 2016a)
L17E IWLTALKFLGKHAAKHEAKQQLSKL (Akishiba et al. 2017)
lactoferrampin(265- 284) DLIWKLLSKAQEKFGKNKSR (Reyes-Cortes et al. 2017)
lactoferricin(17-30) FKCRRWQWRMKKLG (Reyes-Cortes et al. 2017)
lactoferrin(19-40) KCFMWQEMLNKAGVPKLRCARK (Duchardt et al. 2009)
LAH1 KKLALALALALHALALALALKKA (Moulay et al. 2017)
LALF(31-52) HYRIKPTFRRLKWKYKGKFW (Yanez et al. 2017)
LB FKCRRWQWRMKKLGAPSITCVRRAF) (Liu et al. 2013b)
L-CPP LAGRRRRRRRRRK (Liu et al. 2006)
LDP-NLS KWRRKLKKLRPKKKRKV (Ponnappan and Chugh, 2017)
LE10 LELELELELELELELELELE (Antunes et al. 2013)
LF chimera FKCRRWQWRMKKLG-K-RSKNKGFKEQAKSLLKWILD (Reyes-Cortes et al. 2017)
linTT1 AKRGARSTA (Hunt et al. 2017)
LK LKKLLKLLKKLLKLAG (Kim et al. 2016b)
LL37 LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES (Kim et al. 2016b)
LLIIL LLIIL (Alaybeyoglu et al. 2017)
LMWP VSRRRRRRGGRRRR (Chen et al. 2017d)
LP-12 HIITDPNMAEYL (Kumar et al. 2015)
LPAs RCnRCnK (Gupta et al. 2011)
LTV LTVSPWY (Chopra 2012)
lycosin-I RKGWFKAMKSIAKFIAKEKLKEHL (Tan et al. 2017)
Lyp1 CGNKRTRGC (Fogal et al. 2008)
M918 MVTVLFRRLRIRRACGPPRVRV (El-Andaloussi et al. 2007)
Maurocalcine GDCLPHLKLCKENKGCCSKKCKRRGTNIEKRCR (Poillot et al. 2010)
MAP KLALKLALKALKAALKLA (Oehlke et al. 1998)
MAP12 LKTLTETLKELTKTLTEL (Oehlke et al. 2002)
MCoTI-I polycyclic SGSDGGVCPKILQRCRRDSDCPGACICRGNGYCG (Camarero, 2017)
MCoTI-II polycyclic CPKILKKCRRDSDCPGACICRGNGYCGSGSDGGV (Huang et al. 2015)
MFK MFKLRAKIKVRLRAKIKL (Samuels et al. 2017)
Mgpe9 CRRLRHLRHHYRRRWHRFRC (Vij et al. 2016a)
MitP INLKKLAKL(Aib)KKIL (Howl et al. 2018)
m(KLA)-iRGD klaklakklakla-K-GG-iRGD (Qifan et al. 2016)
MMGP1 MLWSASMRIFASAFSTRGLGTRMLMYCSLPSRCWRK (Pushpanathan et al. 2013)
MPER fragment ELDKWASLWNWFDITNWLWYIK (Song et al. 2009)
MPG GALFLGFLGAAGSTMGA cysteamide (Morris et al. 1997)
MPG GALFLGFLGAAGSTMGASQPKKKRKV cycteamide (Deshayes et al. 2005)
MPG-8 AFLGWLGAWGTMGWSPKKKRK (Crombez et al. 2009b)
mRVG YTIWMPENPRPGTPCDIFTKSRGKRASNGGGRRRRRRRRR (Villa-Cedillo et al. 2017)
MT23 LPKQKRRQRRRM (Zhou et al. 2017)
mtCPP1 r-Dmt-OF (Cerrato et al. 2015)
MTM AAVALLPAVLLALLAP (Fletcher et al. 2010)
MTD84 AVALVAVVAVA (Lim et al. 2014)
MTP MLSLRQSIRFFK (Chuah et al. 2015a, b)
MTS KGEGAAVLLPVLLAAPG (Zhao et al. 2001)
MTS1 AAVLLPVLLAAP (Rojas et al. 1998)
Mut3DPT-C9h VKKKKIKAEIKIYVETLDDIFEQWAHSEDL (de la Torre et al. 2017)
Myr-ApoE Myr-LRKLRKRLLR (Tajik-Ahmadabad et al. 2017)
New modalities Polycyclic, hairpin, stapled peptides for delivery (Valeur et al. 2017, Waldmann et al. 2017)
NF1 Stearyl-AGY(PO3)LLGKTNLKALAALAKKIL (Arukuusk et al. 2013)
NF51 δ-(Stearyl-AGYLLG)OINLKALAALAKKIL (Arukuusk et al. 2013)
NF55 δ-(Stearyl-AGYLLG)OINLKALAALAKAIL (Freimann et al. 2016)
NLS PKKKRKV (Yoneda et al. 1992).
NLS-StAx-h stapled RRWPRXILDXHVRRVWR (Dietrich et al. 2017)
NoLS KKRTLRKNDRKKRC (Yao et al. 2015)
Novicidin KNLRRIIRKGIHIIKKYF (Milosavljevic et al. 2016)
NPFSD VLTNENPFSDP (Gong et al. 2016)
NYAD-1 stapled ITFEDLLDYYGP (Zhang et al. 2008)
Oct4-PTD DVVRVWFCNRRQKGKR (Adachi et al. 2017)
P007 Ac-(RAhxR)4-Ahx-βAla (Greer et al. 2014)
P1 LRRWSLG (Peng et al. 2017b)
P2 WKRTLRRL (Peng et al. 2017b)
P3 YGRKKRRQR (Tan et al. 2006)
P7 RRMKWKK (Watson et al. 2017)
P11 YGRKKRRQRRR (Zhao et al. 2011)
P11 HSDVHK (Bang et al. 2011)
P11LRR P11LRR (Li et al. 2010)
P14LRR (PLPRPR)4 (Brezden et al. 2016)
p18 LSTAADMQGVVTDGMASG (Taylor et al. 2009)
P21 KRKKKGKGLGKKRDPCLRKYK (Dixon et al. 2016)
P28 LSTAADMQGVVTDGMASGLDKDYLKPDD, Leu50-Asp77 of azurin (Yamada et al. 2016)
p28 FLHSGTAVTCTYPALTPQWEGSDCTHRL (Signorelli et al. 2017)
p53 peptide MO6 Stapled TSF*EYWYLL* (Chee et al. 2014)
PAF26 Ac-rkkwfw (Lopez-Garcia et al. 2002)
PAS GKPILFF (Woldetsadik et al. 2017)
pCLIP6 KVRVRVRVpP(pT)RVRERVK (Chen et al. 2017b)
pD-SP5 riPRPSPKMGV(pS)VS (Chen et al. 2017b)
PenetraMax KWFKIQMQIRRWKNKR, L- and D- (Khafagy el et al. 2015)
Penetratin RQIKIWFQNRRMKWKK (Derossi et al. 1994)
Pep-1 KETWWETWWTEWSQPKKKRKV cysteamide (Morris et al. 1997)
pepM KLFMALVAFLRFLTIPPTAGILKRWGTI (Freire et al. 2014)
pepR LKRWGTIKKSKAINVLRGFRKEIGRMLNILNRRRR (Freire et al. 2014)
Pept1 PLILLRLLRGQF (Marks et al. 2011)
Peptide 599 GLFEAIEGFIENGWEGMIDGWYGGGGRRRRRRRRRK (Alexander-Bryant et al. 2015)
Pep42 Cyclic CTVALPGGYVRVC (Kim et al. 2006)
PepNeg SGTQEEY (Neves-Coelho et al. 2017)
PepFect6 Stearyl-AGYLLGK(εTMQ)INLKALAALAKKIL, PF6 (El-Andaloussi et al. 2011)
PepFect14 Stearyl- AGYLLGKLLOOLAAAALOOLL (Ezzat et al. 2011)
PG1 RGGRLCYCRRRFCVCVGR (Liu et al. 2013b)
pHLIP AEQNPIY-WARYADWLFTTPLLLLDLALLV-DADEGT (Andreev et al. 2010)
PHPs H6-H10 peptides (Kimura et al. 2017)
PIP1 RXRRXRRXRIKILFQNRRMKWKK (Ivanova et al. 2008)
Pip5e RXRRBRRXRILFQYRXRBRXRB (Betts et al. 2012)
Pip6a Ac-RXRRBRRXRYQFLIRXRBRXRB (Lehto et al. 2014)
POD CGGG(ARKKAAKA)4 (Dasari et al. 2017)
PR9 FFLIPKG-R9 (Liu et al. 2013a)
PTD YARVRRRGPRRR (Dong et al. 2016)
PTD3 R9-ETWWETWWTEW (Kizaka-Kondoh et al. 2009)
PTD4 YARAAARQARA (McCusker et al. 2007)
Poly-Arg Most popular R7 – R12 (Mitchell et al. 2000, Futaki, 2006)
pVEC LLIILRRRIRKQAHAHSK (Elmquist et al. 2001)
Pyrrhocoricin VDKGSYLPRPTPPRPIYNRN (Otvos et al. 2000)
R4K1 Stapled Ac-RRRRKS*LHRS*LQDS (Speltz et al. 2018)
R6dGR R6dGR (Wang et al. 2017)
R8 R8 (Wender et al. 2001)
R8-dGR R8dGR (Liu et al. 2016b)
R9-H4A2 Ac-YR9-HAHAHH (Okitsu et al. 2017)
R6W3 R6W3 (Bechara et al. 2013)
R10W6 R10W6 (Bechara et al. 2013)
RA9 RRAARRARR (Alhakamy et al. 2013)
RALA WEARLARALARALARHLARALARALRACEA (McCarthy et al. 2014)
RDP CKSVRTWNEI IPSKGCLRVG GRCHPHVNGG GRRRRRRRRC (Xiao et al. 2017)
REDV REDV (Yang et al. 2016)
RF GLKKLARLFHKLLKLGC (Yang et al. 2014)
cRGDfC Cyclic RGDfC (Wada et al. 2017)
iRGD Cyclic CRGDKGPDC (Peng and Kopecek, 2015)
RGE RGERPPR (Yu et al. 2017)
RH9 RRHHRRHRR (Alhakamy et al. 2013)
RL9 RRLLRRLRR (Alhakamy et al. 2013)
RL16 RRLRRLLRRLLRRLRR (Joanne et al. 2009)
RT53 RQIKIWFQNRRMKWKKAKLNAEKLKDFKIRLQYFARGLQV YIRQLRLALQGKT (Jagot-Lacoussiere et al. 2016)
RTP004 RKKRRQRRRG-K15-GRKKRRQRRR) (Lee et al. 2015a)
RV24 RRRRRRRRRGPGVTWTPQAWFQWV (Lo and Wang, 2012)
RVG YTIWMPENPRPGTPCDIFTNSRGKRASNG (Kumar et al. 2007)
RVG-9R YTIWMPENPRPGTPCDIFTNSRGKRASNGGGGRRRRRRRRR (Rassu et al. 2017)
RVG29 YTIWMPENPRPGTPCDIFTNSRGKRASNGGGGRRRRRRRRR (Villa-Cedillo et al. 2017)
RW9 RRWWRRWRR (Alhakamy et al. 2013)
RW16 RRWRRWWRRWWRRWRR (Jobin et al. 2013)
(RXR)4 (R-Ahx-R)4 (Saleh et al. 2010)
(rXr)4 (r-Ahx-r)4 (Vij et al. 2016b)
S155 VKKKKIKREI-KIAAQRYGRELRRMADEFHV (Haidar et al. 2017)
S4(13)-PV ALWKTLLKKVLKAPKKKRKV (Mano et al. 2007)
SAP VRLPPPVRLPPPVRLPPP (Pujals et al. 2006)
SAP(E) VELPPPVELPPPVELPPP (Martin et al. 2011)
all-D-SAP (vrlppp)3 (Pujals et al. 2007)
SAPSp-lipo stearyl-GGGGHGAHEHAGHEHAAGEHHAHE (Suzuki et al. 2017)
SAR6EW SAR6EW (Im et al. 2017)
sC18 GLRKRLRKFRNKIKEK (Oren et al. 1999)
(sC18)2 (GLRKRLRKFRNKIKEK)2 (Gronewold et al. 2017)
SMTP motif, LRLLR (Fuselier and Wimley, 2017)
SPACE Cyclic ACTGSTQHQCG (Hsu and Mitragotri, 2011)
SRCRP2-11 GRVEVLYRGSW (Tuttolomondo et al. 2017)
STR-KV H3K3V6 (Pan et al. 2016)
SS-02 Dmt-r-FK (Alta et al. 2017)
SS-20 F-r-FK (Alta et al. 2017)
SS-31 r-Dmt-KF (Zhao et al. 2005)
SynB1 RGGRLSYSRRRFSTSTGR (Rousselle et al. 2000)
T2 LVGVFH (Kumar et al. 2012)
Tat(49-57) RKKRRQRRR (Vives et al. 1997a)
Tat(48-60) GRKKRRQRRRPPQ (Vives et al. 1997b)
Tat(44-57) CGISYGRKKRRQRRR (Niesner et al. 2002)
Tat(37-72) CFITKALGISYGRKKRRQRRRPPQGSQT-HQVSLSKQ (Fawell et al. 1994)
Tat analog GRKKRRQR (Nguyen et al. 2008)
Tat-LK15 Tat-KLLKLLLKLLLKLLK (Peng et al. 2017a)
TCTP MIIFRALISHKK (Bae et al. 2016)
TD-1 ACSSSPSKHCG (Chen et al. 2006)
TD2.2 SYWYRIVLSRTGRNGRLRVGRERPVLGESP (Heffernan et al. 2012)
TH peptide GYLLGHINLHHLAHL-Aib-HHIL (Chen et al. 2017a)
TM2 PKKGSKKAVTKAQKKDGA (Kochurani et al. 2015)
Transportan GWTLNSAGYLLGKINLKALAALAKKIL, TP (Pooga et al. 1998)
TP10 AGYLLGKINLKALAALAKKIL (Soomets et al. 2000)
TPk VRRFkWWWkFLRR (Bahnsen et al. 2015)
Tpl KWCFRVCYRGICYRRCRGK (Jain et al. 2015)
TPP TKDNNLLGRFELSG (Gehrmann et al. 2014)
TT1 CKRGARSTA (Paasonen et al. 2016)
vAMP 059 INWKKWWQVFYTVV (Dias et al. 2017)
vCPP 0769 RRLTLRQLLGLGSRRRRRSR (Dias et al. 2017)
vCPP 2319 WRRRYRRWRRRRRWRRRPRR (Dias et al. 2017)
VDAC(1-26) MAVPPTYADLGKSARDVFTKGYGFGL (Smilansky et al. 2015)
VP22 NAATATRGRSAASRPTQRPRAPARSASRPRRPVQ (Elliott and O’Hare, 1997)
V peptide TVDNPASTTNKDKLFAVRK (Manosroi et al. 2014)
VT5 DPKGDPKGVTVTVTVTVTGKGDPKPD (Oehlke et al. 1997)
W(RW)4 W(RW)4 (Nasrolahi Shirazi et al. 2013)
Xentry LCLR (Montrose et al. 2014)
X-pep MAARLC (Adachi et al. 2017)
YKA YKALRISRKLAK (Desai et al. 2014)
YTA2 YTAIAWVKAFIRKLRK (Lindgren et al. 2006)
YTA4 IAWVKAFIRKLRKGPLG (Lindgren et al. 2006)
Z2 FWIGGFIKKLKRSKLA (Chen et al. 2017c)
Z3 FKIKKFIGGLWRSKLA (Chen et al. 2017c)
Z12 KRYKNRVASRKCRAKFKQLLQHYREVAAAKSSENDRLRLLLK (Derouazi et al. 2015)
ZXR-1 FKIGGFIKKLWRSKLA (Chen et al. 2017c)

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How to form the fibrillary structure using beta-amyloid peptides?

Aβ-(1–42) was dissolved to 1 mM in 100% hexafluoroisopropanol, hexafluoroisopropanol was removed under vacuum, and the peptide was stored at −20 °C. For the aggregation protocols, the peptide was first resuspended in dry Me2SO (DMSO) to 5 mM. For oligomeric conditions, F-12 (without phenol red) culture media was added to bring the peptide to a final concentration of 100 μM, and the peptide was incubated at 4 °C for 24 h. For fibrillar conditions, 10 mM HCl was added to bring the peptide to a final concentration of 100 μM, and the peptide was incubated for 24 h at 37 °C. ADDLS, amyloid derived diffusible ligands.

Aducanumab is a human monoclonal antibody that has been studied for the treatment of Alzheimer’s disease.

A click chemistry was reported about the formation of azides from primary amines

Click chemistry for drug screening

A click chemistry was reported about the formation of azides from primary amines. This powerful tool enables the reaction of just one equivalent of a simple diazotizing species, and fluorosulfuryl azide (FSO2N3), for the preparation of over 1,200 azides on 96-well plates in a safe and practical manner. This method greatly expands the number of accessible azides and 1,2,3-triazoles because the primary amine is one of the most abundant functional groups in small compounds, proteins and antibodies.

The method opens the door for numerous applications in drug screening and discovery. The cell penetration peptides can be easily introduced to conjugate with any azide containing drugs, compounds, antibodies, or proteins.

The cell penetration peptides (CPPs) are capable of delivering biologically active cargo to the cell interior. The desired therapeutic cargo could be attached to a CPP using the copper free click chemistry and then delivered to an intracellular target, thereby overcoming the entry restrictions set by the plasma membrane.

Braftide, a 10mer peptide synthesized at LifeTein, a potent allosteric inhibitor of BRAF dimer for cancer therapy

Dabrafenib


BRAF is an RAF kinase. It is a core component of the RAS/RAF/MEK/ERK signaling cascade, known as mitogen-activated protein kinase (MAPK) pathway. It is one of the major effectors of oncogene RAS, and is often mutated in human cancer cells.


Two FDA approved drugs, Dabrafenib, and vemurafenib, effectively inhibit the most common BRAF variant V600E, a monomeric BRAF. But, the non-V600E BRAF mutations are intrinsically resistant to these drugs. These drugs may also paradoxically stimulate the pathway when the tumor cells contain wild-type BRAF and oncogenic RAS, causing secondary malignancies.
The researchers tried to tackle the dimeric BRAF. The dimeric BRAF, such as the wild type and G469A, a most prevalent non-V600E variant in lung cancer cells, hinges on dimer interface (DIF), a 20aa span near the tail end of the alpha-C helix of BRAF. The researchers designed Braftide using computational modeling, aiming to block the dimerization. They tested the functionality in vitro, in HEK263 cells and colon cancer cell lines.

LifeTein synthesized Braftide (TRHVNILLFM), Null-Braftide (THHVNILLFM), Cy3-Braftide (TRHVNILLFM-Cy3), TAT-Braftide (GRKKRRQRRRPQ-PEG-TRHVNILLFM), and TAT (GRKKRRQRRRPQ). We reviewed here some of the assays that helped support Braftide as an allosteric inhibitor of BRAF dimer and down-regulator of MAPK signaling pathway for cancer therapy.


1) Cell-free in vitro assay: dose-response curve. First of all, the researchers show that Braftide has a sub-micromolar IC50 for dimeric BRAF. Full-length dimeric BRAF-WT and BRAF-G469A (from HEK293F cells) were used for dose-response curves, and the BRAF activity was probed by pMEK production.


2) Cell-free in vitro assay: Saturation binding assay. The researchers used Cy3-labeled Braftide (Cy3-Braftide) to characterize (KD) the binding of Braftide with dimeric BRAF-WT using fluorescence quantification.


3) Cell-free in vitro assay: Immunoprecipitation (IP). The purpose of IP was to show Braftide disrupted the BRAF dimerization. Braftide was added to HEK293 cell lysate coexpressing V5- and FLAG-tagged BRAF-WT. FLAG-tagged BRAF was pulled down by FLAG antibody-conjugated resin, which was further probed for V5-tagged BRAF. Braftide indeed reduced homodimer BRAF.


4) Delivery of Braftide into HEK cell for BRAF inhibition. Braftide was tagged with cell-penetrating peptide TAT. TAT-Braftide (and its negative control TAT alone) was used to treat HEK293 cells transiently transfected with BRAF-WT and BRAF-G469A. Four hours of treatment resulted in reductions of BRAF, pMEK, MEK (i.e. the MAPK pathway), which were analyzed with respective antibodies by immunoblotting.


5) Delivery of Braftide into cancer cells for BRAF inhibition and cell proliferation inhibition. Two colon cancer cell lines (KRAS-G13D-colon carcinoma) were treated with cell-penetrating TAT-Braftide and assayed for the inhibition of BRAF activity, down-regulation of MAPK signaling, and cell proliferation. All were shown positive, while the negative control TAT alone were negative.

https://pubs.acs.org/doi/abs/10.1021/acschembio.9b00191

LifeTein’s Synthetic Scorpion Toxin Peptides Helped Scientists Unravel Chronic Pain Mechanisms

Synthetic Scorpion Toxin Peptides
Synthetic Wasabi Receptor Toxin

LifeTein’s synthetic Wasabi Receptor Toxin, Wasabi Receptor Toxin Mutants, Biotinylated Wasabi Receptor Toxin, and AlexaFluor-488 conjugated Wasabi Receptor Toxin and Mutants helped scientists unravel chronic pain mechanisms.

Researchers at the University of California, San Francisco (UCSF) have identified a scorpion toxin that targets the “wasabi receptor”. The wasabi receptor is an ion channel protein that is responsible for the sinus-clearing or eye-stinging pain experienced when eating wasabi or chopping onions.

It was found that the scorpion toxin, a peptide as the wasabi receptor toxin, or WaTx, activates the wasabi receptor TRPA1 and triggers this pain response to irritants. The WaTx peptide is a novel cell-penetrating peptide and can directly pass through the plasma membrane, without needing to traverse through channel proteins.

The WaTx peptide could be used to study chronic pain and inflammation and may lead to the development of novel non-opioid pain therapies. WaTx produces pain and pain hypersensitivity, but not neurogenic inflammation.

Reference: Lin King, J. V., Emrick, J. J., Kelly, M. J. S., Herzig, V., King, G. F., Medzihradszky, K. F., & Julius, D. (2019). A Cell-Penetrating Scorpion Toxin Enables Mode-Specific Modulation of TRPA1 and Pain. Cell. doi:10.1016/j.cell.2019.07.014

LifeTein peptide FLAG(GS)HA: DYKDDDDK-GGGGS-YPYDVPDYA-NH2 helped discover insulin-like peptide6, Dilp6, in regulating growth in fruit flies Drosophila

FLAG and HA tagged IGF1

In humans, liver-derived insulin-like growth factor (IGF1) drives postnatal growth. Early childhood infection of E. coli, Campylobacter spp., even asymptomatic, reduces IGF1 level and restricts early-childhood growth. Does the pathogen-induced Toll-like innate immune signaling contribute to growth restriction? To answer the question, the researchers examined a corresponding pathway in fruit flies.

In fruit flies, Dilps (Drosophila insulin-like peptides) drive their growth, for example, the growth rate of imaginal discs which give rise to adult structures such as wings. Dilps share homology with insulin and IGF1, and they bind to the insulin receptor. Dilp6 is produced by fat body, an organ for nutrient storage and immune functions.

The researchers found Dilp6 is a selective target of Toll signaling in the fat body, an innate immune response from bacterial infections. They also found that Toll signaling reduces Dilp6 transcripts, and dramatically suppresses circulatory Dilp6 levels, and restricts whole-body growth. Restoring Dilp6, on the other hand, rescues growth and viability in fruit flies even with active Toll signaling.

LifeTein’s peptide FLAG(GS)HA was used as a standard in ELISA to quantify Dilp6 in fruit fly hemolymph samples. Here, Dilp6 was tagged with FLAG and HA because of FLAG- and HA-tagged Dilp6HF allele from CRISPR/CAS9. In this ELISA assay, the plate wells were coated with anti-FLAG antibody, then FLAG(GS)HA or fruit fly hemolymph sample were added to the wells. FLAG(GS)HA and FLAG- and HA-tagged Dilp6 were quantified by anti-HA-Peroxidase 3F10 antibody and subsequent chromogenic reaction. For more details of the method, see the section “Hemolymph Dilp6 measurements by ELISA” in the link.

https://www.sciencedirect.com/science/article/pii/S2211124719309052

The smaller ions (F- and Cl-, 50mM NaF and NaCl solutions) tend to stabilize β-sheets

Peptide amphiphiles are composed of hydrophobic alkyl tails and peptide regions designed to self-assemble into cylindrical supramolecular nanofibers in solution. While some β-sheets are formed by hydrogen bonds between short β-strands (2 or 3 residues) others are formed by extended β-strands.

The strongly-hydrated ions (F- and Cl-) are more attracted to the positively charged lysine residues on the surface of the peptide nanofiber. When peptide residues form β-sheets, an F- or Cl- ion forms a salt bridge between the side chains of lysine residues from two neighboring peptide amphiphile chains. The salt bridge stabilizes the peptide by bringing the backbones closer, which in turn results in a transition from random coil to extended β-sheets structures. The smaller ions (F- and Cl-, 50mM NaF and NaCl solutions) tend to stabilize β-sheets slightly better compared to the larger ions (I-, Br-).

So self-assembly of peptide amphiphiles into supramolecular nanofibers can be regulated by modifying the salt solution.

Reference: doi.org/10.1021/acs.jpcb.9b05532

Self-Assembling Peptide Hydrogel as a Versatile Drug Delivery Platform

Peptide Hydrogel

Hydrogels with a capacity to absorb and hold water within a porous, swelled structure make it a great candidate as a drug delivery system due to their broad range of physical properties as well as chemical adaptability. For example, a positively charged polypeptide (poly-l-lysine, PLL) coupling to a self-assembling dipeptide (Fmoc-FF) leads to the formation of hydrogels with rheological properties suitable for injection.

Hydrogenation via self-assembly is a hierarchical process. The hydrogels can be easily prepared via simple mixing and incorporated with various stoichiometric ratios of peptides without any additional synthetic processes. Peptides can form hydrogels by multiple non-covalent interactions. It was found that PTZ-Gly-Phe-Phe-Tyr can form gels at ultra-low concentrations of 0.01 wt.%. The π-π stacking may be another driving forces in the self-assembly to form the final hydrogel structure. The N-cadherin mimic peptide (CLRAHAVDIN) and TGF-β1 mimic peptide (CESPLKRQ) synthesized by LifeTein were used to form an injectable 3D hydrogel. Increased retention of stem cells by using an injectable hydrogel has resulted in successful tissue engineering outcomes.

Another efficient method to facilitate hydrogel formation is based on the electrostatic attraction of oppositely charged peptides. The order of amino acids is of great importance for hydrogenation. Self-assembling beta-hairpin peptides, with high arginine content, exhibited extremely good performance in killing bacteria. The peptide hydrogels also have been demonstrated to be used as wound healing agents and other therapeutic instruments under different conditions. Curcumin could be encapsulated into hairpin hydrogels as an injectable agent for localized delivery.