Abraham Patchornik: The Contemporary Relevance of His Work for Chemistry and Biology

JACS Au, Год журнала: 2024, Номер unknown

Опубликована: Дек. 20, 2024

Abraham Patchornik was born in 1926 Ness Ziona, a town Palestine founded by his great-grandfather Reuben Lehrer 1883. He started to study chemistry as an undergraduate at the Hebrew University. However, this interrupted war, and he completed studies various locations West Jerusalem. From 1952 1956 PhD (new) Weizmann Institute of Science with Ephraim Katchalski. After postdoc NIH, returned 1958, when joined Department Biophysics. In 1972-1979, became chairman new Organic Chemistry Weizmann, own research geared toward applying creative solve biological problems. passed away hometown Ziona 2014. conceptual leader peptide polymer chemistry. Given importance selective functional group protection for construction oligomeric molecules, interested using "nonstandard", orthogonal purpose, i.e. photosensitive protecting groups (PPGs) place thermal reactions. It R.B. Woodward who suggested strategy 1965, while on sabbatical leave Harvard. it not until that idea versatile PPG enable multistep synthesis realized. Here, we provide account early co-workers developed, immense impact they have had fields. particular, survey use PPGs live cell physiology (i.e., caged compounds), development gene chips via light-directed solid-phase synthesis. Further, highlight recent work "photochemical delivery" drugs, otherwise termed photopharmacology. Finally, discuss relationship between compounds how contemporary neuroscience uses genetically encoded chromophores control function.

Язык: Английский

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An opioid efficacy switch for reversible optical control of peripheral analgesia

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 20, 2024

Abstract The mu-opioid receptor (MOR) is a major target for the treatment of pain. However, opioids are prone to side effects which limit their effectiveness as analgesics and can lead opioid use disorders or, even, lethal overdose. systemic administration agonists makes it both very difficult decipher underlying circuit mechanisms action drug specific subpopulations isolate therapeutic from adverse effects. Here we design, synthesize, characterize reversibly photoswitchable morphinan agonist termed “azo-morphine-3” ( AM-3 ) interconverts low high efficacy in response different wavelengths light enable optical control MOR signaling. Cryo-EM structures “ trans ” cis states bound reveal distinct binding modes azobenzene moiety, each inducing unique structural dynamics, providing insight into molecular basis efficacy. In mice, drives reversible repeatable anti-nociception with reduced effect profile owing its restriction periphery ability be locally activated at site

Язык: Английский

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The Dorsal Raphe as a Regulator of Emotion and Reward: Beyond Pain

Biological Psychiatry, Год журнала: 2023, Номер 94(11), С. 834 - 835

Опубликована: Окт. 30, 2023

Язык: Английский

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