abstract
Self-assembly of short peptides has emerged as an interesting research field for a wide range of applications. Recently, several truncated fragments of long-chain peptides or proteins responsible for different neurodegenerative diseases were studied to understand whether they can mimic the property and function of native peptides or not. It was reported that such a kind of peptide adopts a beta-sheet structure in the disease state. It was observed that aromatic amino acid-rich peptide fragments possess a high tendency to adopt a beta-sheet conformation. In this article, we are first time reporting the crystal structure of two tetrapeptides: Boc-GAII-OMe (Peptide 1) and Boc-GGVV-OMe (Peptide 2), composed of aliphatic amino acids, and the sequences are similar to the A beta-peptide fragments A beta(29-32) and A beta(37-40), respectively. In the solid-state, they are self-assembled in an antiparallel beta-sheet fashion. The peptide units are connected by the strong amide hydrogen-bonding (N-H center dot center dot center dot O) interactions. Apart from that, other noncovalent interactions are also present, which help to stabilize the cross-beta-sheet arrangement. Interestingly, in the crystal structure of Peptide 1, noncovalent C center dot center dot center dot C interaction between the electron-deficient carbonyl carbon, and the electron-rich sp(3)-carbon atom is observed, which is quite rare in the literature. The calculated torsion angles for these peptides are lying in the beta-sheet region of the Ramachandran plot. FT-IR studies also indicate the formation of an antiparallel beta-sheet structure in the solid-state. Circular dichroism of the peptides in the aqueous solution also suggests the presence of predominantly beta-sheet-like conformation in the aqueous solution. Under cross-polarized light, Congo Red stained both peptides showed green-gold color due to birefringence indicating their amyloidogenic nature. This result indicates that the short peptide composed of aliphatic amino acid is capable of forming a beta-sheet structure in the absence of aromatic amino acid and also can mimic the function of the native amyloid peptide.
keywords
SELF-ASSEMBLING PEPTIDE; FIBRIL FORMATION; DOUBLE HELIX; AMINO-ACID; HYDROGEL; PROTEIN; POLYPEPTIDE; TRIPEPTIDE; DESIGN; MODULATION
subject category
Chemistry, Physical
authors
Misra, S; Singh, P; Mahata, RN; Brandao, P; Roy, S; Mahapatra, AK; Nanda, J
our authors
Paula Cristina Ferreira da Silva Brandão
Assistant Researcheracknowledgements
This work is supported by a DST-INSPIRE Faculty (IFA16CH246) grant (to J.N.). J.N. gratefully acknowledges the support of the Department of Chemistry, IIEST-Shibpur. We are thankful to Dr. Jishu Naskar and Mr. Satyabrata Samui for the microscopic study. We are also thankful Dr. Arindam Saha for WPXRD study.