Synthesis of beta-peptides with beta-helices from new C-linked carbo-beta-amino acids: study on the impact of carbohydrate side chains.
The design and synthesis of beta-peptides from new C-linked carbo-beta-amino acids (beta-Caa) presented here, provides an opportunity to understand the impact of carbohydrate side chains on the formation and stability of helical structures. The beta-amino acids, Boc-(S)-beta-Caa((g))-OMe 1 and Boc-(R)-beta-Caa((g))-OMe 2, having a D-galactopyranoside side chain were prepared from D-galactose. Similarly, the homo C-linked carbo-beta-amino acids (beta-hCaa); Boc-(S)-beta-hCaa((x))-OMe 3 and Boc-(R)-beta-hCaa((x))-OMe 4, were prepared from D-glucose. The peptides derived from the above monomers were investigated by NMR, CD, and MD studies. The beta-peptides, especially the shorter ones obtained from the epimeric (at the amine stereocenter C(beta)) 1 and 2 by the concept of alternating chirality, showed a much smaller propensity to form 10/12-helices. This substantial destabilization of the helix could be attributed to the bulkier D-galactopyranoside side chain. Our efforts to prepare peptides with alternating 3 and 4 were unsuccessful. However, the beta-peptides derived from alternating geometrically heterochiral (at C(beta)) 4 and Boc-(R)-beta-Caa((x))-OMe 5 (D-xylose side chain) display robust right-handed 10/12-helices, while the mixed peptides with alternating 4 and Boc-beta-hGly-OMe 6 (beta-homoglycine), resulted in left-handed beta-helices. These observations show a distinct influence of the side chains on helix formation as well as their stability.
Sharma
Gangavaram V M
GV
Discovery Laboratory, Organic Chemistry Division III, Indian Institute of Chemical Technology, Hyderabad 500 007, India. esmvee@iict.res.in
Rao
Kota Sudhakar
KS
Ravi
Rapolu
R
Narsimulu
Kongari
K
Nagendar
Pendem
P
Chandramouli
Chirutha
C
Kumar
Singarapu Kiran
SK
Kunwar
Ajit C
AC
D000596:Amino Acids / Q000737:chemistry*; D002241:Carbohydrates / Q000138:chemical synthesis / Q000737:chemistry*; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013237:Stereoisomerism
D000596:Amino Acids; D002241:Carbohydrates; D010455:Peptides