Novel beta- and gamma-Amino Acid-Derived Inhibitors of Prostate-Specific Membrane Antigen
DC Field | Value | Language |
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dc.contributor.author | Kim, Kyul | - |
dc.contributor.author | Kwon, Hongmok | - |
dc.contributor.author | Barinka, Cyril | - |
dc.contributor.author | Motlova, Lucia | - |
dc.contributor.author | Nam, SangJin | - |
dc.contributor.author | Choi, Doyoung | - |
dc.contributor.author | Ha, Hyunsoo | - |
dc.contributor.author | Nam, Hwanhee | - |
dc.contributor.author | Son, Sang-Hyun | - |
dc.contributor.author | Minn, Il | - |
dc.contributor.author | Pomper, Martin G. | - |
dc.contributor.author | Yang, Xing | - |
dc.contributor.author | Kutil, Zsofia | - |
dc.contributor.author | Byun, Youngjoo | - |
dc.date.accessioned | 2021-08-31T05:59:41Z | - |
dc.date.available | 2021-08-31T05:59:41Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2020-03-26 | - |
dc.identifier.issn | 0022-2623 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/57219 | - |
dc.description.abstract | Prostate-specific membrane antigen (PSMA) is an excellent biomarker for the early diagnosis of prostate cancer progression and metastasis. The most promising PSMA-targeted agents in the clinical phase are based on the Lys-urea-Glu motif, in which Lys and Glu are alpha-(L)-amino acids. In this study, we aimed to determine the effect of beta- and gamma-amino acids in the S1 pocket on the binding affinity for PSMA. We synthesized and evaluated the beta- and gamma-amino acid analogues with (S)- or (R)-configuration with keeping alpha-(L)-Glu as the S1'-binding pharmacophore. The structure-activity relationship studies identified that compound 13c, a beta-amino acid analogue with (R)-configuration, exhibited the most potent PSMA inhibitory activity with an IC50 value of 3.97 nM. The X-ray crystal structure of PSMA in complex with 13c provided a mechanistic basis for the stereochemical preference of PSMA, which can guide the development of future PSMA inhibitors. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | AMER CHEMICAL SOC | - |
dc.subject | GLUTAMATE-CARBOXYPEPTIDASE-II | - |
dc.subject | UREA-BASED INHIBITORS | - |
dc.subject | PRECLINICAL EVALUATION | - |
dc.subject | PSMA INHIBITOR | - |
dc.subject | HIGH-AFFINITY | - |
dc.subject | CANCER | - |
dc.subject | THERAPY | - |
dc.subject | LIGANDS | - |
dc.subject | DESIGN | - |
dc.subject | ENDORADIOTHERAPY | - |
dc.title | Novel beta- and gamma-Amino Acid-Derived Inhibitors of Prostate-Specific Membrane Antigen | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Byun, Youngjoo | - |
dc.identifier.doi | 10.1021/acs.jmedchem.9b02022 | - |
dc.identifier.scopusid | 2-s2.0-85082542708 | - |
dc.identifier.wosid | 000526404600035 | - |
dc.identifier.bibliographicCitation | JOURNAL OF MEDICINAL CHEMISTRY, v.63, no.6, pp.3261 - 3273 | - |
dc.relation.isPartOf | JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.citation.title | JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.citation.volume | 63 | - |
dc.citation.number | 6 | - |
dc.citation.startPage | 3261 | - |
dc.citation.endPage | 3273 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Medicinal | - |
dc.subject.keywordPlus | GLUTAMATE-CARBOXYPEPTIDASE-II | - |
dc.subject.keywordPlus | UREA-BASED INHIBITORS | - |
dc.subject.keywordPlus | PRECLINICAL EVALUATION | - |
dc.subject.keywordPlus | PSMA INHIBITOR | - |
dc.subject.keywordPlus | HIGH-AFFINITY | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | THERAPY | - |
dc.subject.keywordPlus | LIGANDS | - |
dc.subject.keywordPlus | DESIGN | - |
dc.subject.keywordPlus | ENDORADIOTHERAPY | - |
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