silaproline and neurotensin-(8-13)

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.

Topics: Animals; Cell Membrane; COS Cells; Crystallography, X-Ray; Models, Molecular; Neurotensin; Nuclear Magnetic Resonance, Biomolecular; Organosilicon Compounds; Peptide Fragments; Proline; Protein Conformation; Stereoisomerism