Studies on novel peptidomimetics having bi-directional dispositions of hydroxylated D-Pro-Gly motifs anchored on a C(2)-symmetric iminosugar-based foundation.
A rigid pyrrolidine based scaffold comprising of 2,5-dideoxy-2,5-imino-D-idaric acid (1) is developed. Attachment of peptide strands to the carboxylic groups at both ends of this novel template led to the peptidomimetics 2 and 3. Conformational analysis by NMR studies revealed that compounds 2b, 3b and 2c, 3c take interesting turn structures (C(2) symmetric for 2c and 3c) in DMSO-d(6) consisting of identical intramolecular hydrogen bonds at two ends between LeuNH --> sugar-OH as depicted in structure A, whereas 2a and 3a display structures with regular beta-turns with hydrogen bonds between LeuNH --> Boc-C=O in one-half of their molecular frameworks (structure B), characteristic of the turn structures commonly observed in "D-Pro-Gly"-containing peptides. These results suggest that a cis hydroxyl group at the 3-position of the proline residue favors a pseudo beta-turn-like nine-membered ring structure in hydroxyproline-containing peptides involving an intramolecular hydrogen bond between the hydroxyl and the i + 2 backbone amide.
Chakraborty
T K
TK
Indian Institute of Chemical Technology, Hyderabad 500 007, India. chakraborty@iict.ap.nic.in
Srinivasu
P
P
Kumar
S Kiran
SK
Kunwar
A C
AC
D002855:Chromatography, Thin Layer; D004151:Dipeptides / Q000737:chemistry*; D006860:Hydrogen Bonding; D006909:Hydroxyproline / Q000737:chemistry; D050112:Imino Pyranoses; D009682:Magnetic Resonance Spectroscopy; D018716:Molecular Mimicry; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D011392:Proline / Q000737:chemistry; D011487:Protein Conformation; D011759:Pyrrolidines / Q000737:chemistry; D013329:Structure-Activity Relationship; D013400:Sugar Acids / Q000737:chemistry*
C459299:2,5-dideoxy-2,5-iminoidaric acid; D004151:Dipeptides; D050112:Imino Pyranoses; D010455:Peptides; D011759:Pyrrolidines; D013400:Sugar Acids; C057749:prolylglycine; D011392:Proline; D006909:Hydroxyproline