Furanoid sugar amino acids as dipeptide mimics in design of analogs of vasoactive intestinal peptide receptor binding inhibitor.
In this study we describe the development of peptidomimetic analogs of the potent vasoactive intestinal peptide receptor binding inhibitor, Leu(1) -Met(2) -Tyr(3) -Pro(4) -Thr(5) -Tyr(6) -Leu(7) -Lys(8) -OH 1, by incorporating furanoid sugar amino acids (SAAs) 2-4 into the molecule. The furanoid SAAs 2-4 were used as dipeptide isosteres to replace Tyr(3) -Pro(4) or Pro(4) -Thr(5) in sequence 1. The resulting analogs 5-9 were tested for their anti-cancer activities in vitro, following the standard MTT assay on a panel of human cancer cell lines. One of the potent analogs, 6a was tested in vivo for tumor regression on primary colon tumor xenografted nude mice. Our experimental results suggest that many of these analogs show either retention or enhancement of biological activity.
Dabur Research Foundation, Sahibabad, Ghaziabad, India. sprasad@dabur.com
S
S
Prasad
A
A
Mathur
M
M
Jaggi
R
R
Sharma
N
N
Gupta
V R
VR
Reddy
G
G
Sudhakar
S U
SU
Kumar
S K
SK
Kumar
A C
AC
Kunwar
T K
TK
Chakraborty
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004151:Dipeptides / Q000737:chemistry*; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D018716:Molecular Mimicry; D010447:Peptide Hydrolases; D018005:Receptors, Vasoactive Intestinal Peptide / Q000032:analysis / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D014183:Transplantation, Heterologous
D000596:Amino Acids; D004151:Dipeptides; D005663:Furans; D018005:Receptors, Vasoactive Intestinal Peptide; D010447:Peptide Hydrolases; D012697:Serine Endopeptidases