Influence of Silaproline on Peptide Conformation and Bioactivity

Abstract

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.

Efficient Synthesis of Nicotianamine and Non‐Natural Analogues

“…We then extended this strategy to produce three synthetic analogues (Figure 2) by replacing the carboxy-azetidine ring with proline (10), silaproline (11) [18] and pyroglutamic acid (12), thus modifying the physicochemical properties of the molecules. These compounds were used as probes in plant experiments.…”

Bioactive Amino Acids, Peptides and Peptidomimetics Containing Silicon

“…This structure retained biological activity and was much more stable toward enzymatic degradation than nonsilane congeners [3].…”

“…Many other silicon-containing amino acids have been prepared during the intervening years and these have been broadly investigated [2]. Among these interesting non-natural amino acids, an intestively studied analog is sila-proline 2 [3]. In contrast, the elusive amino acid 3 has only been prepared as a derivative of the parent structure and its limited stability has precluded extensive investigation [4].…”

Incorporation of β‐Silicon‐β3‐Amino Acids in the Antimicrobial Peptide Alamethicin Provides a 20‐Fold Increase in Membrane Permeabilization

“…[2] The unique propertieso fs ilicon-containing amino acids, such as increased lipophilicity, [3] make them desirable synthetic targets.C onsiderablee fforts in this fieldo fr esearch has focused on the synthesis of silicon-containing a-amino acids with silicon in either the a-o rb-position (Figure1). The first example of b-trimethylsilyl alanine 1 synthesis was published in 1956.…”