Gutenberg Open Science: Ligand-based design of selective peptidomimetic uPA and TMPRSS2 inhibitors with arg bioisosteres

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-10222

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DC Field	Value	Language
dc.contributor.author	Müller, Patrick	-
dc.contributor.author	Zimmer, Collin	-
dc.contributor.author	Frey, Ariane	-
dc.contributor.author	Holzmann, Gideon	-
dc.contributor.author	Weldert, Annabelle Carolin	-
dc.contributor.author	Schirmeister, Tanja	-
dc.date.accessioned	2024-03-15T07:45:35Z	-
dc.date.available	2024-03-15T07:45:35Z	-
dc.date.issued	2024	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/10240	-
dc.description.abstract	Trypsin-like serine proteases are involved in many important physiological processes like blood coagulation and remodeling of the extracellular matrix. On the other hand, they are also associated with pathological conditions. The urokinase-pwlasminogen activator (uPA), which is involved in tissue remodeling, can increase the metastatic behavior of various cancer types when overexpressed and dysregulated. Another member of this protease class that received attention during the SARS-CoV 2 pandemic is TMPRSS2. It is a transmembrane serine protease, which enables cell entry of the coronavirus by processing its spike protein. A variety of different inhibitors have been published against both proteases. However, the selectivity over other trypsin-like serine proteases remains a major challenge. In the current study, we replaced the arginine moiety at the P1 site of peptidomimetic inhibitors with different bioisosteres. Enzyme inhibition studies revealed that the phenylguanidine moiety in the P1 site led to strong affinity for TMPRSS2, whereas the cyclohexylguanidine derivate potently inhibited uPA. Both inhibitors exhibited high selectivity over other structurally similar and physiologically important proteases.	en_GB
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	540 Chemie	de_DE
dc.subject.ddc	540 Chemistry and allied sciences	en_GB
dc.title	Ligand-based design of selective peptidomimetic uPA and TMPRSS2 inhibitors with arg bioisosteres	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-10222	-
jgu.type.contenttype	Scientific article	de
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 09 Chemie, Pharmazie u. Geowissensch.	de
jgu.organisation.number	7950	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	International journal of molecular sciences	de
jgu.journal.volume	25	de
jgu.journal.issue	3	de
jgu.pages.alternative	1375	de
jgu.publisher.year	2024	-
jgu.publisher.name	MDPI	de
jgu.publisher.place	Basel	de
jgu.publisher.issn	1422-0067	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	540	de
jgu.publisher.doi	10.3390/ijms25031375	de
jgu.organisation.ror	https://ror.org/023b0x485	-
jgu.subject.dfg	Lebenswissenschaften	de
Appears in collections:	DFG-491381577-G

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