Structural similarity between β(3)-peptides synthesized from β(3)-homo-amino acids and aspartic acid monomers.
Formation of stable secondary structures by oligomers that mimic natural peptides is a key asset for enhanced biological response. Here we show that oligomeric β(3)-hexapeptides synthesized from L-aspartic acid monomers (β(3)-peptides 1, 5a, and 6) or homologated β(3)-amino acids (β(3)-peptide 2), fold into similar stable 14-helical secondary structures in solution, except that the former form right-handed 14-helix and the later form left-handed 14-helix. β(3)-Peptides from L-Asp monomers contain an additional amide bond in the side chains that provides opportunities for more hydrogen bonding. However, based on the NMR solution structures, we found that β(3)-peptide from L-Asp monomers (1) and from homologated amino acids (2) form similar structures with no additional side-chain interactions. These results suggest that the β(3)-peptides derived from L-Asp are promising peptide-mimetics that can be readily synthesized using L-Asp monomers as well as the right-handed 14-helical conformation of these β(3)-peptides (such as 1 and 6) may prove beneficial in the design of mimics for right-handed α-helix of α-peptides.
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada, T6G 2E1; Department of Pharmacognosy and Medicinal Chemistry, Faculty of Pharmacy, Taibah University, Al-Madinah Al-munawarah, 41477, Kingdom of Saudi Arabia.
Sahar
S
Ahmed
Tara
T
Sprules
Kamaljit
K
Kaur
D001224:Aspartic Acid / Q000737:chemistry*; D002942:Circular Dichroism; D015195:Drug Design; D009682:Magnetic Resonance Spectroscopy; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D060327:Solid-Phase Synthesis Techniques; D012996:Solutions; D040681:Structural Homology, Protein; D014867:Water / Q000737:chemistry
D010455:Peptides; D012996:Solutions; D014867:Water; D001224:Aspartic Acid
14-helical structure; l-aspartic acid monomers; solution conformation; β3-peptides