Influence of silaproline on peptide conformation and bioactivity.
The analogue gamma-(dimethylsila)-proline, denoted silaproline (Sip), was synthesized in both enantiomerically pure forms by diastereoselective alkylation of a chiral glycine equivalent with use of Schöllkopf's bis-lactim ether method. The effect of replacing a proline residue in model peptides by this new proline surrogate has been examined in the crystal state by X-ray diffraction and in solution by IR absorption and NMR techniques. Silaproline and proline-containing sequences exhibit very similar conformational properties. Silaproline was also substituted for proline in a neurotensin (8-13) analogue that retained biological activity and exhibited enhanced resistance to biodegradation.
Cavelier
Florine
F
Laboratoire des Amino acides, Peptides et Protéines, UMR-CNRS 5810, Universités de Montpellier I et II, UM II, CC19-34095 Montpellier Cedex 05, France.
Vivet
Bertrand
B
Martinez
Jean
J
Aubry
André
A
Didierjean
Claude
C
Vicherat
André
A
Marraud
Michel
M
D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D009496:Neurotensin / Q000737:chemistry* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D017646:Organosilicon Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D013237:Stereoisomerism
D017646:Organosilicon Compounds; D010446:Peptide Fragments; C455420:silaproline; D009496:Neurotensin; C054381:neurotensin (8-13); D011392:Proline