Triggering HIV polyprotein processing by light using rapid photodegradation of a tight-binding protease inhibitor

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F15%3A10314968" target="_blank" >RIV/00216208:11310/15:10314968 - isvavai.cz</a>

Alternative codes found

RIV/61388963:_____/15:00443993

Result on the web

<a href="http://dx.doi.org/10.1038/ncomms7461" target="_blank" >http://dx.doi.org/10.1038/ncomms7461</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/ncomms7461" target="_blank" >10.1038/ncomms7461</a>

Result language

angličtina

Original language name

Triggering HIV polyprotein processing by light using rapid photodegradation of a tight-binding protease inhibitor

Original language description

HIV protease (PR) is required for proteolytic maturation in the late phase of HIV replication and represents a prime therapeutic target. The regulation and kinetics of viral polyprotein processing and maturation are currently not understood in detail. Here we design, synthesize, validate and apply a potent, photodegradable HIV PR inhibitor to achieve synchronized induction of proteolysis. The compound exhibits subnanomolar inhibition in vitro. Its photolabile moiety is released on light irradiation, reducing the inhibitory potential by 4 orders of magnitude. We determine the structure of the PR-inhibitor complex, analyze its photolytic products, and show that the enzymatic activity of inhibited PR can be fully restored on inhibitor photolysis. We alsodemonstrate that proteolysis of immature HIV particles produced in the presence of the inhibitor can be rapidly triggered by light enabling thus to analyze the timing, regulation and spatial requirements of viral processing in real time.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

CE - Biochemistry

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2015

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Nature Communications

ISSN

2041-1723

e-ISSN

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Volume of the periodical

6

Issue of the periodical within the volume

09 March 2015

Country of publishing house

GB - UNITED KINGDOM

Number of pages

8

Pages from-to

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UT code for WoS article

000352697100002

EID of the result in the Scopus database

2-s2.0-84924390132