Structure-activity relationship studies of prostate-specific membrane antigen (PSMA) inhibitors derived from α-amino acid with (S)- or (R)-configuration at P1′ region
Prostate-specific membrane antigen (PSMA), a type II membrane glycoprotein, is considered an excellent target for the diagnosis or treatment of prostate cancer. We previously investigated the effect of β- and γ-amino acids with (S)- or (R)-configuration in the S1 pocket on the binding affinity for PSMA. However, comprehensive studies on the effect of α-amino acid with (R)-configuration in the S1′ pocket has not been reported yet. We selected ZJ-43 (1) and DCIBzL (5) as templates and synthesized their analogues with (S)- or (R)-configuration in the P1 and P1′ regions. The PSMA-inhibitory activities of compounds with altered chirality in the P1′ region were dropped dramatically, with their IC50 values changing from nM to μM ranges. The compounds with (S)-configuration at both P1 and P1′ regions were more potent than the others. The findings of this study may provide insights regarding the structural modification of PSMA inhibitor in the S1′ binding pocket.
Structural and computational basis for potent inhibition of glutamate carboxypeptidase II by carbamate-based inhibitors
A series of carbamate-based inhibitors of glutamate carboxypeptidase II (GCPII) were designed and synthesized using ZJ-43, N-[[[(1S)-1-carboxy-3-methylbutyl]amino]carbonyl]-L-glutamic acid, as a molecular template in order to better understand the impact
Barinka, Cyril,Novakova, Zora,Hin, Niyada,Bím, Daniel,Ferraris, Dana V.,Duvall, Bridget,Kabarriti, Gabriel,Tsukamoto, Reiji,Budesinsky, Milos,Motlova, Lucia,Rojas, Camilo,Slusher, Barbara S.,Rokob, Tibor András,Rulí?ek, Lubomír,Tsukamoto, Takashi
Site-Selective, Late-Stage C?H 18F-Fluorination on Unprotected Peptides for Positron Emission Tomography Imaging
Peptides are often ideal ligands for diagnostic molecular imaging due to their ease of synthesis and tuneable targeting properties. However, labelling unmodified peptides with 18F for positron emission tomography (PET) imaging presents a number of challenges. Here we show the combination of photoactivated sodium decatungstate and [18F]-N-fluorobenzenesulfonimide effects site-selective 18F-fluorination at the branched position in leucine residues in unprotected and unaltered peptides. This streamlined process provides a means to directly convert native peptides into PET imaging agents under mild aqueous conditions, enabling rapid discovery and development of peptide-based molecular imaging tools.
Yuan, Zheliang,Nodwell, Matthew B.,Yang, Hua,Malik, Noeen,Merkens, Helen,Bénard, Fran?ois,Martin, Rainer E.,Schaffer, Paul,Britton, Robert
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p. 12733 - 12736
(2018/09/12)
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