Abstract
Protein tyrosine phosphatase 1B (PTP1B) is implicated as a negative regulator of insulin receptor (IR) signaling and a potential drug target for the treatment of type II diabetes and other associated metabolic syndromes. Therefore, small molecular inhibitors of PTP1B can be considered as an attractive approach for the design of new therapeutic agents of type II diabetes diseases. In a continuing search for new protein phosphatase inhibitors from fungi, we have isolated a new compound, named penostatin J (1), together with three known ones, penostatin C (2), penostatin A (3), and penostatin B (4), from cultures of the entomogenous fungus Isaria tenuipes. The structure of penostatin J (1) was elucidated by extensive spectroscopic analysis. We also demonstrate for the first time that penostatin derivatives exhibit the best PTP1B inhibitory action. These findings suggest that penostatin derivatives are a potential novel kind of PTP1B inhibitors.
Highlights
Tyrosine phosphorylation and dephosphorylation are crucial elements in eukaryotic signal transduction [1]
The protein tyrosine phosphatase (PTP) superfamily are divided into more than three families: (i) ‘classical PTPs’, which exist both as transmembrane forms and non-transmembrane forms; (ii) the dual-specificity phosphatases, which are able to dephosphorylate both phosphotyrosine and phosphothreonine in specific sequence contexts; (iii) the low molecular weight phosphotyrosine protein phosphatases (LMW-PTPs) [3,4]
Inhibitors of Protein tyrosine phosphatase 1B (PTP1B) can be considered as an attractive approach for the design of new therapeutic agents for the treatment of type II diabetes and new antitumoral drugs
Summary
Tyrosine phosphorylation and dephosphorylation are crucial elements in eukaryotic signal transduction [1]. Inhibitors of PTP1B can be considered as an attractive approach for the design of new therapeutic agents for the treatment of type II diabetes and new antitumoral drugs. To date very few inhibitors have isolated from microorganisms, insect pathogenic fungi [8]. Insect pathogenic fungi have been considered as an untapped source of small molecules PTP inhibitors. Interest in searching for bioactive compounds from insect pathogenic fungi has increased considerably recently [14,15]. In a continuing search for new PTP1B inhibitors from insect pathogenic fungi, we have isolated a new compound, named penostatin J (1), together with the known ones penostatin C (2), penostatin A (3), and penostatin B (4) (Figure 1) from cultures of the entomogenous fungi Isaria tenuipes. Details of the isolation and structural elucidation of 1 are reported
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
