Serine Protease Inhibition by a Silanediol Peptidomimetic

Abstract

Silanediol peptidomimetics are demonstrated to inhibit a serine protease. Asymmetric synthesis of the inhibitor was accomplished using Brown hydroboration and CBS reduction of an acylsilane intermediate. The silanediol product was found to inhibit the serine protease chymotrypsin with a Ki of 107 nM. Inhibition of the enzyme may involve exchange of a silane hydroxyl with the active site serine nucleophile, contrasting with previous silanediol protease inhibitors.

Hydroxymethylsilanetriol – A Simple Analog of Silicic Acid

“…It is probable that in the culture solution a slow transformation of hydroxymethylsilanetriol to silicic acid occurred which maintained culture growth, but clearly without incorporation of oxymethylene units into the diatom frustule. On the other hand, the inhibitory effect can be explained by inhibition of a protease-type enzyme, perhaps by a mechanism similar to that recently postulated for peptidometic silanediols by Sieburth [35]. Carboxyethylsilanetriol had no effect on cultures either containing or deficient in silicic acid.…”

Design and expeditious synthesis of organosilanes as potent antivirals targeting multidrug-resistant influenza A viruses

“…Compound 1 is a silanediol peptidomimetic and was designed as a serine protease inhibitor. [29] Compound 2 is an octahedral silicon complex and was designed as a DNA intercalator. [30] Compound 3 is a Si-rhodamine that emits in the near infrared region.…”

“…2, compound 1 ). [29] (2) organosilanes can go beyond tetrahedral coordination to octahedral coordination (Fig. 2, compound 2 ) and such compounds can be used as DNA chelators.…”

Iron‐Catalyzed Intermolecular 1,2‐Difunctionalization of Styrenes and Conjugated Alkenes with Silanes and Nucleophiles

“…[1,2] Specifically,t he recently expanding studies of both silicon analogues of known drugs and entirely new silicon-containing compounds have become an emerging leading research field in the pharmaceutical industry.F or example,1 -amino-2silylalkanes exhibit fascinating biological activities which exist in many potential pharmaceuticals and drug lead compounds, [2] such as Sila-venlafaxine (1), [2a,b] the compound 2, [2c] and TMS-alanine (3 [2d,e] ;F igure 1). [1,2] Specifically,t he recently expanding studies of both silicon analogues of known drugs and entirely new silicon-containing compounds have become an emerging leading research field in the pharmaceutical industry.F or example,1 -amino-2silylalkanes exhibit fascinating biological activities which exist in many potential pharmaceuticals and drug lead compounds, [2] such as Sila-venlafaxine (1), [2a,b] the compound 2, [2c] and TMS-alanine (3 [2d,e] ;F igure 1).…”

“…(1), silanes (2)and Cnucleophiles (3). Thereaction is initiated by akey silicon-centered radical from oxidative cleavage of the Si À Hb ond followed by addition across the C=Cb ond in addition to NÀHo xidative functionalization cascades,t hus building the 1-amino-2-silylalkane cores.M oreover,t he reaction can be expanded to threecomponent 1,2-carbosilylation of alkenes by SiÀH/CÀH oxidative functionalization.…”