How does the amino acid sequence of a protein chain determine and remain its 3D folded state? How do small proteins fold?
Short Peptide Folding
Many small proteins or miniproteins are peptides shorter than 40-50 residues with stable folding that contain secondary structure elements such as alpha helices and beta strands.
An autonomously folding, 35 residue, thermostable subdomain (HP36) of the villin headpiece, is the smallest folded domain of a naturally occurring protein. So, polypeptides simplify the protein-folding problem. It allows in-depth examinations of sequence-structure-stability relationships without using the complex larger proteins.
In this recent study, Rocklin et al. designed sequences intended to fold into desired structures. The novel proteins may be useful in bioengineering or pharmacological applications.
Check the paper from here: https://goo.gl/Tregb7
Proteins and most naturally occurring peptides are composed of amino acids in the L-configuration. However, D-amino acids have been detected in a variety of peptides synthesized in animal cells. Examples include opiate and antimicrobial peptides from frog skin, neuropeptides from snails, hormones from crustaceans, and venom from spiders. These D amino acid peptides are considered to be the most promising alternative for anticancer, anti-inflammatory, antimicrobial, and delivery agents.
About D-Amino Acid Peptides
The design of all-D-peptides has been applied to increase bioactive peptides’ resistance to endogenous enzymes, as well as their bioavailability. Retro-inverso peptides are obtained by replacing the standard L-amino acid residues with the corresponding D-amino acids and reversing the direction of the peptide backbone. Therefore, the original spatial orientation and the chirality of the side chains is unchanged. This results in a non-complementary side chain topochemistry between the analog and the parental L-peptide. The significantly improved biostability of D-peptides usually leads to longer in vivo circulation half-time, making the D-peptide based drug delivery system more attractive and efficient than their L-peptide counterparts.
Success has been achieved immunologically in using retro-inverso peptides toward antigenic mimicry of their parent l-peptides. It was found that the retro-all-d-peptide isomer of p53(15–29), like its parent l-peptide, adopted a right-handed helical conformation in the complex. However, in some cases, the retro-inverso isomers are significantly inferior to their parent l-peptides. The low cellular uptake of D-peptides remain an unmet challenge.
So the best way is to insert some key D amino acids into the peptide sequence. For example, some pharmaceutical important peptide antibiotics such as gramicidins, actinomycins, or bacitracins incorporate D-amino acids into the drug design. The assemblies of D-peptides deserve further exploration and may lead to more surprises.
D amino acid peptide with high stability
See more details from here: http://lifetein.com/Peptide-Synthesis-D-Amino-Acid.html