Protoporphyrin IX/Cobyrinate Derived Hybrids – Novel Activators of Soluble Guanylyl Cyclase

Abstract

A new cobyrinate/protoporphyrin IX molecular hybrids were prepared via CuAAC reaction. The synthesis involved selective preparation of cobyrinate and PpIX derived building blocks possessing respectively terminal alkyne and azide moieties followed by the CuOAc catalyzed cycloaddition reaction. Synthesized molecules activated soluble guanylyl cyclase showing strong linker length/activation dependence.

Recent trends in the development of vitamin B12derivatives for medicinal applications

“…54,55 In a related but distinct strategy for developing B 12 -based therapeutics, the design of dysfunctional B 12 analogues encounters an encouraging renaissance and aims toward the development of new classes of antibacterial and antiproliferative agents (chapter 2.3). [60][61][62] In all four approaches, the basic properties of B 12 are explored for obtaining compounds with new behaviour and functions. [60][61][62] In all four approaches, the basic properties of B 12 are explored for obtaining compounds with new behaviour and functions.…”

“…33,62 For this purpose, cobyrinic acid and PpIX were connected to each other with linkers of different compositions and lengths. 33,62 For this purpose, cobyrinic acid and PpIX were connected to each other with linkers of different compositions and lengths.…”

Towards NO‐free Regulation of sGC: Design and Synthesis of trans‐AB‐porphyrins

“…It has been reported that PPIX derivatives possessing only one free propionic acid group are still able to activate sGC 11. Thus, at the beginning of our work on the synthetic PPIX analogues, we designed a simple trans ‐AB‐ meso ‐substituted porphyrin 11 , substituted with the carboxymethyl group at position 5 and with an alkyl chain at position 15.…”

“…sGC assay :11 Purified sGC (0.5 μg at 1 mg mL −1 ) was dissolved in 60 μL of triethanolamine (65 mM), EGTA (415 μM), albumin (0.5 mg mL −1 ), cGMP (4 mM), creatine kinase (0.25 mg mL −1 ), creatine phosphate (20 mM), and magnesium chloride (7.5 mM)) and was provided with the indicated concentrations of meso ‐substituted porphyrins. After 10 minutes incubation at room temperature, 40 μL of 500 μM GTP/0.08 μCi of [α‐32P]GTP, ∼ 150,000 cpm) was added to initiate the cGMP formation and the sample was heated to 37 °C.…”

The Red Color of Life Transformed – Synthetic Advances and Emerging Applications of Protoporphyrin IX in Chemical Biology

“…[33b], Examples are the incorporation of PPIX into polymeric materials, some of them with potential application in antimicrobial PDT,[68c], synthesis of porphyrins with altered physicochemical properties and the preparation of a PPIX‐cobyrinate dyad as an activator of soluble guanylyl cyclase . Ester formation on PPIX was achieved using EDC and DMAP[77a], [77b], or CDI[68c] and the respective hydroxyl‐substituted substrate to yield mono‐ and diesters 47 and 48 . Alternatively, esterification of PPIX acid moieties and cellulose hydroxyl groups was achieved by treatment with p ‐toluenesulfonyl chloride ( p ‐TsCl) in pyridine (Scheme ).…”