Kyle A Totaro

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1-Ethyl-3-(3-(dimethylamino)propyl)carbodiimide (EDC) bioconjugations have been utilized in preparing variants for medical research. While there have been advances in optimizing the reaction for aqueous applications, there has been limited focus toward identifying conditions and side reactions that interfere with product formation. We present a systematic(More)
The 20S core particle of the proteasome in Mycobacterium tuberculosis (Mtb) is a promising, yet unconventional, drug target. This multimeric peptidase is not essential, yet degrades proteins that have become damaged and toxic via reactions with nitric oxide (and/or the associated reactive nitrogen intermediates) produced during the host immune response.(More)
A chemistry for the facile two-component macrocyclization of unprotected peptide isocyanates is described. Starting from peptides containing two glutamic acid γ-hydrazide residues, isocyanates can be readily accessed and cyclized with hydrazides of dicarboxylic acids. The choice of a nucleophilic linker allows for the facile modulation of biochemical(More)
This paper reports the synthesis of a 3-hydroxypropyl analog of HMPA. This ligand will be coordinated to SmI2, and kinetic studies are performed. This is worthy of study because the protonation step of the reduction mechanism, which typically occurs intermolecularly in SmI2-mediated reductions of carbonyls, will occur intramolecularly; thus, the potential(More)
Peptides containing N2-acyl piperazic or 1,6-dehydropiperazic acids can be formed efficiently via a novel multicomponent reaction of 1,4,5,6-tetrahydropyridazines, isocyanides, and carboxylic acids. Remarkably, the reaction's induced intramolecularity can enable the regiospecific formation of products with N2-acyl piperazic acid, which counters the(More)
Natural products that inhibit the proteasome have been fruitful starting points for the development of drug candidates. Those of the syringolin family have been underexploited in this context. Using the published model for substrate mimicry by the syringolins and knowledge about the substrate preferences of the proteolytic subunits of the human proteasome,(More)
We demonstrate that the Ugi reaction enables chemoselective derivatization of biological amines, carboxylic acids, aldehydes, or ketones with a chromophore under one set of reaction conditions, even in the presence of water. Derivatization of neurotransmitters, hormones, disease biomarkers and other metabolites bodes well for systems biology and diagnostic(More)
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