Synthesis and conformational studies of peptides from new C-linked carbo-beta-amino acids (beta-Caas) with anomeric methylamino- and difluorophenyl moieties.
New C-linked carbo-beta-amino acids (beta-Caas), Cbz-(S)-beta-Caa-(NHBoc)-OMe (1) and Cbz-(R)-beta-Caa-(NHBoc)-OMe (2), with an additional amine group (methylamino group of NHBoc) at the C-1 position of the lyxofuranoside side chain and Boc-(S)-beta-Caa-(diFP)-OMe (3) and Boc-(R)-beta-Caa-(diFP)-OMe (4), with a C-difluorophenyl (diFP) moiety at the anomeric position of the lyxofuranoside side chain were prepared from D-mannose. Beta-peptides [tetra- and hexapeptides] were synthesized from these beta-Caas, 'epimeric' [at the amine stereocentre (C(beta))], using the concept of 'alternating chirality' to carry out their conformational studies [NMR (CDCl(3)), CD and MD]. In the monomer design, it was envisaged that the presence of an additional amine group in 1 or 2 would help in solubilizing the peptides in water, while, the C-difluorophenyl (diFP) moiety of 3 and 4 is expected to enhance the biological activity. The peptides having 1 and 2, though could not retain their 12-10-mixed helices in water, have shown moderate activity against gram positive and gram negative bacterial strains. The peptides prepared from 3 and 4, much against our expectations, did not display any biological activity.
Sharma
Gangavaram V M
GV
D-211, Discovery Laboratory, Organic Chemistry Division III, Hyderabad, 500 007, India. esmvee@iict.res.in
Subash
Velaparthi
V
Reddy
Nelli Yella
NY
Narsimulu
Kongari
K
Ravi
Rapolu
R
Jadhav
Vivekanand B
VB
Murthy
Upadhyayula S N
US
Kishore
Kankipati Hara
KH
Kunwar
Ajit C
AC
D000596:Amino Acids / Q000737:chemistry*; D001419:Bacteria / Q000187:drug effects; D015195:Drug Design; D005461:Fluorine / Q000737:chemistry*; D008745:Methylation; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation
D000596:Amino Acids; D010455:Peptides; D005461:Fluorine