236414-37-2

Upstream product

• 26093-31-2 7-amino-4-methylcoumarin. 
• 2389-60-8 Z-Lys(Boc)-OH 
• 71989-26-9 Fmoc-Lys(tert-butoxycarbonyl) 
• 263368-34-9 (9H-fluoren-9-yl)methyl-tert-butyl (6-((4-methyl-2-oxo-2H-chromen-7-yl)amino)-6-oxohexane-1,5-diyl)-(S)-dicarbamate 
• 501-53-1 benzyl chloroformate 
• 222037-62-9 tert-butyl (S)-(5-amino-6-((4-methyl-2-oxo-2H-chromen-7-yl)-amino)-6-oxohexyl) carbamate 

Downstream Products

• 154497-24-2 (S)-benzyl (6-amino-1-((4-methyl-2-oxo-2H-chromen-7-yl)amino)-1-oxohexan-2-yl)carbamate 

Relevant academic research and scientific papers

Development of Peptide-Based Sirtuin Defatty-Acylase Inhibitors Identified by the Fluorescence Probe, SFP3, That Can Efficiently Measure Defatty-Acylase Activity of Sirtuin

Sirtuins (SIRTs) are a family of nicotinamide adenine dinucleotide-dependent histone deacetylases that serve as epigenetic regulators of many physiological processes. Recent studies have shown that in addition to their well-known deacetylase activity, sir

Interactions between sirtuins and fluorogenic small-molecule substrates offer insights into inhibitor design

Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent lysine deacylases regulating metabolism and stress responses and are involved in human pathologies such as neurodegeneration. In this study, four fluorogenic small-molecule substrates, i.e., acetyl-(AcBKA), crotonyl-(CrBKA), succinyl-(SuBKA), and myristoyl-(MyBKA)-containing substrates, were synthesized and tested against three representative sirtuin isoforms (i.e., SIRT2, SIRT5, and SIRT6). Enzyme kinetic results indicate that the fluorogenic small-molecule substrates have similar sirtuin-isoform preference as compared to peptide substrates. ITC analyses reveal that AcBKA or MyBKA binding to SIRT2 is mainly driven by entropy, whereas SuBKA binding to SIRT5 is driven by enthalpy. The SIRT5:SuBKA complex crystal structure reveals a new substrate-binding mode that is different from peptide substrate binding modes, but involves Tyr102, Arg105, and other catalytically important residues on Loop S; this indicates that SuBKA is desuccinylated by SIRT5 probably through the catalytic mechanism proposed for peptide substrates. The biophysical and structural results presented herein will provide thermodynamic insights and key pharmacophore features for the development of selective sirtuin isoform-specific inhibitors.

Inhibitors of the NAD+-dependent protein desuccinylase and demalonylase sirt5

NAD+-dependent histone deacetylases (sirtuins) play important roles in epigenetic regulation but also through nonhistone substrates for other key cellular events and have been linked to the pathogenesis of cancer, neurodegeneration, and metabol

Slow-binding inhibition of peptide deformylase by cyclic peptidomimetics as revealed by a new spectrophotometric assay

A new spectrophotometric/fluorimetric assay for peptide deformylase (PDF) has been developed by coupling the PDF reaction with that of dipeptidyl peptidase I (DPPI) and using N-formyl-Met-Lys-AMC as substrate. Removal of the N-terminal formyl group by PDF renders the dipeptide an efficient substrate of DPPI, which subsequently removes the dipeptidyl units to release 7-amino-4-methylcoumarin as the chromophore/fluorophore. The PDF reaction is conveniently monitored on a UV-Vis spectrophotometer or a fluorimeter in a continuous fashion. The utility of the assay was demonstrated by determining the catalytic activity of PDF and the inhibition constants of PDF inhibitors. These studies revealed the slow-binding behavior of a previously reported macrocyclic PDF inhibitor. This method offers several advantages over the existing PDF assays and should be particularly useful for screening PDF inhibitors in the continuous fashion.