220400-04-4Relevant articles and documents
Dual-Mechanism Quenched Fluorogenic Probe Provides Selective and Rapid Detection of Cathepsin L Activity**
Schleyer, Kelton A.,Fetrow, Ben,Zannes Fatland, Peter,Liu, Jun,Chaaban, Maya,Ma, Biwu,Cui, Lina
, p. 1082 - 1087 (2021)
Cathepsin L (CTL) is a cysteine protease demonstrating upregulated activity in many disease states. Overlapping substrate specificity makes selective detection of CTL activity difficult to parse from that of its close homologue CTV and the ubiquitous CTB. Current probes of CTL activity have limited applications due to either poor contrast or extra assay steps required to achieve selectivity. We have developed a fluorogenic probe, CTLAP, that displays good selectivity for CTL over CTB and CTV while exhibiting low background fluorescence attributed to dual quenching mechanisms. CTLAP achieves optimum CTL selectivity in the first 10 min of incubation, thus suggesting that it is amenable for rapid detection of CTL, even in the presence of competing cathepsins.
A protected l-bromophosphonomethylphenylalanine amino acid derivative (BrPmp) for synthesis of irreversible protein tyrosine phosphatase inhibitors
Tulsi, Naresh S.,Downey, A. Michael,Cairo, Christopher W.
experimental part, p. 8679 - 8686 (2011/02/25)
Protein tyrosine phosphatases (PTPs) are important therapeutic targets for medicinal chemists and biochemists. General strategies for the development of inhibitors of these enzymes are needed. Several modular strategies which rely on phosphotyrosine mimics are known for PTP inhibitors. Previous strategies include phosphonomethylphenylalanine (Pmp) derivatives which act as competitive inhibitors. Pmp amino acid derivatives have been used to develop specific inhibitors by incorporation into sequences recognized by the PTP of interest. We report the synthesis of a new phosphonotyrosine analog, l- phosphonobromomethylphenylalanine (BrPmp), which acts as an inhibitor of PTPs. The BrPmp derivative was prepared as an Fmoc-protected amino acid which can be used in standard solid phase peptide synthesis (SPPS) methods. The synthesis of the protected amino acid derivative requires 11 steps from tyrosine with a 30% overall yield. Enzyme inhibition studies with the PTP CD45 demonstrate that BrPmp derivatives are irreversible inhibitors of the enzyme. A tripeptide which incorporated BrPmp had increased inhibitory potency against PTP relative to BrPmp alone, confirming that the incorporation of BrPmp into peptide sequences provides additional context to improve enzyme binding.
Efficient Synthesis of a Phosphinate Bis-Amino Acid and Its Use in the Construction of Amphiphilic Peptides
Lei, Haiyan,Stoakes, Mark S.,Herath, Kamal P. B.,Lee, Jinho,Schwabacher, Alan W.
, p. 4206 - 4210 (2007/10/02)
A new amphiphilic bis-amino acid has been designed and its convergent, asymmetric synthesis achieved in differentially protected form.A convenient preparation of iodophenylalanine, a generally useful starting material, is disclosed.Sequential palladium-catalyzed couplings of aryl iodides to phosphinate lead directly to the target protected bis-amino acid.Controlled peptide coupling of the new bis-amino acid is also demonstrated.
