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Synthesis of β ‐Peptides with β ‐Helices from New C‐Linked Carbo‐ β ‐Amino Acids: Study on the Impact of Carbohydrate Side Chains
Author(s) -
Sharma Gangavaram V. M.,
Rao Kota Sudhakar,
Ravi Rapolu,
Narsimulu Kongari,
Nagendar Pendem,
Chandramouli Chirutha,
Kumar Singarapu Kiran,
Kunwar Ajit C.
Publication year - 2009
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.200800249
Subject(s) - side chain , chemistry , stereochemistry , amino acid , chirality (physics) , helix (gastropod) , monomer , amine gas treating , peptide , stereocenter , biochemistry , organic chemistry , enantioselective synthesis , polymer , catalysis , ecology , quantum mechanics , snail , nambu–jona lasinio model , biology , quark , chiral symmetry breaking , physics
The design and synthesis of β ‐peptides from new C‐linked carbo‐ β ‐amino acids ( β ‐Caa) presented here, provides an opportunity to understand the impact of carbohydrate side chains on the formation and stability of helical structures. The β ‐amino acids, Boc‐( S )‐ β ‐Caa (g) ‐OMe 1 and Boc‐( R )‐ β ‐Caa (g) ‐OMe 2 , having a D ‐galactopyranoside side chain were prepared from D ‐galactose. Similarly, the homo C‐linked carbo‐ β ‐amino acids ( β ‐hCaa); Boc‐( S )‐ β ‐hCaa (x) ‐OMe 3 and Boc‐( R )‐ β ‐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 β ‐peptides, especially the shorter ones obtained from the epimeric (at the amine stereocenter C β ) 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 β ‐peptides derived from alternating geometrically heterochiral (at C β ) 4 and Boc‐( R )‐ β ‐Caa (x) ‐OMe 5 ( D ‐xylose side chain) display robust right‐handed 10/12‐helices, while the mixed peptides with alternating 4 and Boc‐ β ‐hGly‐OMe 6 ( β ‐homoglycine), resulted in left‐handed β ‐helices. These observations show a distinct influence of the side chains on helix formation as well as their stability.