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Keywords = peptidyl fluoromethyl ketones

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16 pages, 4992 KiB  
Review
Current Synthetic Routes to Peptidyl Mono-Fluoromethyl Ketones (FMKs) and Their Applications
by Carissa M. Lloyd, Neil Colgin and Steven L. Cobb
Molecules 2020, 25(23), 5601; https://doi.org/10.3390/molecules25235601 - 28 Nov 2020
Cited by 7 | Viewed by 4393
Abstract
Peptidyl mono-fluoromethyl ketones (FMKs) are a class of biologically active molecules that show potential as both protease inhibitors for the treatment of a range of diseases and as chemical probes for the interrogation of cellular processes. This review describes the current solid- and [...] Read more.
Peptidyl mono-fluoromethyl ketones (FMKs) are a class of biologically active molecules that show potential as both protease inhibitors for the treatment of a range of diseases and as chemical probes for the interrogation of cellular processes. This review describes the current solid- and solution-phase routes employed for the synthesis of peptidyl mono-FMKs. In addition, it provides a brief overview of some of the key applications of FMKs in the fields of chemical biology and medicinal chemistry. Full article
(This article belongs to the Special Issue Advance in Fluorine Chemistry)
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31 pages, 5989 KiB  
Review
Peptidyl Fluoromethyl Ketones and Their Applications in Medicinal Chemistry
by Andrea Citarella and Nicola Micale
Molecules 2020, 25(17), 4031; https://doi.org/10.3390/molecules25174031 - 3 Sep 2020
Cited by 31 | Viewed by 6520
Abstract
Peptidyl fluoromethyl ketones occupy a pivotal role in the current scenario of synthetic chemistry, thanks to their numerous applications as inhibitors of hydrolytic enzymes. The insertion of one or more fluorine atoms adjacent to a C-terminal ketone moiety greatly modifies the physicochemical [...] Read more.
Peptidyl fluoromethyl ketones occupy a pivotal role in the current scenario of synthetic chemistry, thanks to their numerous applications as inhibitors of hydrolytic enzymes. The insertion of one or more fluorine atoms adjacent to a C-terminal ketone moiety greatly modifies the physicochemical properties of the overall substrate, especially by increasing the reactivity of this functionalized carbonyl group toward nucleophiles. The main application of these peptidyl α-fluorinated ketones in medicinal chemistry relies in their ability to strongly and selectively inhibit serine and cysteine proteases. These compounds can be used as probes to study the proteolytic activity of the aforementioned proteases and to elucidate their role in the insurgence and progress on several diseases. Likewise, if the fluorinated methyl ketone moiety is suitably connected to a peptidic backbone, it may confer to the resulting structure an excellent substrate peculiarity and the possibility of being recognized by a specific subclass of human or pathogenic proteases. Therefore, peptidyl fluoromethyl ketones are also currently highly exploited for the target-based design of compounds for the treatment of topical diseases such as various types of cancer and viral infections. Full article
(This article belongs to the Section Medicinal Chemistry)
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