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.
Synthesis and binding studies of two new macrocyclic receptors for the stereoselective recognition of dipeptides
Castilla, Ana Maria,Ballester, Pablo,Conn, M. Morgan
supporting information; experimental part, (2010/07/18)
We present here the design, synthesis, and analysis of a series of receptors for peptide ligands inspired by the hydrogen-bonding pattern of protein β-sheets. The receptors themselves can be regarded as strands 1 and 3 of a three-stranded β-sheet, with crosslinking between the chains through the 4-position of adjacent phenylalanine residues. We also report on the conformational equilibria of these receptors in solution as well as on their tendency to dimerize. 1H NMR titration experiments are used to quantify the dimerization constants, as well as the association constant values of the 1:1 complexes formed between the receptors and a series of diamides and dipeptides. The receptors show moderate levels of selectivity in the molecular recognition of the hydrogen-bonding pattern present in the diamide series, selecting the α-amino acid-related hydrogen-bonding functionality. Only one of the two cyclic receptors shows modest signs of enantioselectivity and moderate diastereoselectivity in the recognition of the enantiomers and diastereoisomers of the Ala-Ala dipeptide (DDG0 1 (DD-DL) = -1.08 kcal/mol and DDG0 1(DD-LD) = -0.89 kcal/mol). Surprisingly, the linear synthetic precursors show higher levels of stereoselectivity than their cyclic counterparts.
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.
Synthesis of the side chain cross-linked tyrosine oligomers dityrosine, trityrosine, and pulcherosine
Skaff, Ojia,Jolliffe, Katrina A.,Hutton, Craig A.
, p. 7353 - 7363 (2007/10/03)
An efficient synthesis of dityrosine and the first syntheses of the tyrosine trimers trityrosine and pulcherosine have been achieved. Protected 3-iodotyrosine underwent tandem Miyaura borylation-Suzuki coupling to give protected dityrosine. The choice of
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.
