55512-69-1

Upstream product

• 539-83-3 β-alanine-(2-mercapto-ethylamide) 
• 599-04-2 (R)-Pantolacton 
• 138148-35-3 D-pantethine 
• 79-83-4 pantothenic acid 
• 60856-63-5 (2R)-(-)-3,3-dimethylbutane-1,2,4-triol 
• 5652-99-3 N-benzyloxycarbonyl-β-alanine-(2-benzylsulfanyl-ethylamide) 
• 100316-90-3 β-alanine-(2-benzylsulfanyl-ethylamide) 
• 104071-84-3 bis-{2-[(N-benzyloxycarbonyl-β-alanyl)-amino]-ethyl}-disulfide 
• 112271-42-8 N,N-phthaloyl-β-alanine-(2-benzylmercapto-ethylamide) 
• 75-75-2 methanesulfonic acid 
• 138148-35-3 bis-(N-pantothenylamidoethyl)disulfide 
• 824393-46-6 3-[N-(9-fluorenyl)methyloxycarbonylamino]-N-(2-tritylsulfanyl-ethyl)-propionamide 
• 875615-42-2 3-[(2,2,5,5-tetramethyl-[1,3]dioxane-4-carbonyl)-amino]-propionic acid 2,5-dioxo-pyrrolidin-1-yl ester 
• 167308-62-5 3-{[(4R)-2,2,5,5-tetramethyl-1,3-dioxan-4-yl]carbonylamino}propionic acid 

Downstream Products

• 16816-68-5 N-D-pantoyl-β-alanine-(2-benzoylmercapto-ethylamide) 
• 82475-06-7 (5R,6R)-3-{2-[3-((R)-2,4-Dihydroxy-3,3-dimethyl-butyrylamino)-propionylamino]-ethylsulfanyl}-6-ethyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester 
• 2226-71-3 D‐pantetheine 4'‐phosphate 
• 639513-14-7 Phosphoric acid (R)-3-(2-{2-[((S)-5-acetylamino-5-carbamoyl-pentylcarbamoyl)-methylsulfanyl]-ethylcarbamoyl}-ethylcarbamoyl)-3-hydroxy-2,2-dimethyl-propyl ester dibenzyl ester 
• 6756-74-7 S-benzoyl coenzyme A 
• 3633-59-8 3′-dephospho-coenzyme A 
• 85-61-0 coenzyme A 
• 85506-43-0 (5R,6R)-3-{2-[3-((S)-2,4-Dihydroxy-3,3-dimethyl-butyrylamino)-propionylamino]-ethylsulfanyl}-6-ethyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitro-benzyl ester 
• 910126-99-7 tetrabenzyl-3,22-dihydroxy-2,2,23,23-tetramethyl-4,8,17,21-tetraoxo-12,13-dithia-5,9,16,20-tetraazatetracosane-1,24-diyl diphosphate 
• 120497-19-0 S-2-(3-[(R)-2,4-dihydroxy-3,3-dimethylbutyrylamino]propionylamino)ethyl (R)-3-hydroxybutanethioate 

Relevant academic research and scientific papers

Gatekeeping Ketosynthases Dictate Initiation of Assembly Line Biosynthesis of Pyrrolic Polyketides

Assembly line biosynthesis of polyketide natural products involves checkpoints where identities of thiotemplated intermediates are verified before polyketide extension reactions are allowed to proceed. Determining what these checkpoints are and how they operate is critical for reprogramming polyketide assembly lines. Here we demonstrate that ketosynthase (KS) domains can perform this gatekeeping role. By comparing the substrate specificities for polyketide synthases that extend pyrrolyl and halogenated pyrrolyl substrates, we find that KS domains that need to differentiate between these two substrates exercise high selectivity. We additionally find that amino acid residues in the KS active site facilitate this selectivity and that these residues are amenable to rational engineering. On the other hand, KS domains that do not need to make selectivity decisions in their native physiological context are substrate-promiscuous. We also provide evidence that delivery of substrates to polyketide synthases by non-native carrier proteins is accompanied by reduced biosynthetic efficiency.

Mechanistic Studies on CysS - A Vitamin B12-Dependent Radical SAM Methyltransferase Involved in the Biosynthesis of the tert-Butyl Group of Cystobactamid

Cobalamin (Cbl)-dependent radical S-adenosylmethionine (SAM) methyltransferases catalyze methylation reactions at non-nucleophilic centers in a wide range of substrates. CysS is a Cbl-dependent radical SAM methyltransferase involved in cystobactamid biosynthesis. This enzyme catalyzes the sequential methylation of a methoxy group to form ethoxy, i-propoxy, s-butoxy, and t-butoxy groups on a p-aminobenzoate peptidyl carrier protein thioester intermediate. This biosynthetic strategy enables the host myxobacterium to biosynthesize a combinatorial antibiotic library of 25 cystobactamid analogues. In this Article, we describe three experiments to elucidate how CysS uses Cbl, SAM, and a [4Fe-4S] cluster to catalyze iterative methylation reactions: a cyclopropylcarbinyl rearrangement was used to trap the substrate radical and to estimate the rate of the radical substitution reaction involved in the methyl transfer; a bromoethoxy analogue was used to explore the active site topography; and deuterium isotope effects on the hydrogen atom abstraction by the adenosyl radical were used to investigate the kinetic significance of the hydrogen atom abstraction. On the basis of these experiments, a revised mechanism for CysS is proposed.

PANTETHEINE DERIVATIVES AND USES THEREOF

The present disclosure relates to compounds of Formula (I), (II), or (II'): (I), (II), (II'), and pharmaceutically acceptable salts or solvates thereof. The present disclosure also relates to pharmaceutical compositions comprising the compounds and therapeutic and diagnostic uses of the compounds and pharmaceutical compositions.

COMPOSITION FOR PROMOTING HAIR GROWTH OR HAIR RESTORATION, CONTAINING NOVEL PANTETHEINE-BASED SUBSTANCE

Provided is a composition for promoting hair growth, containing, as an active ingredient, a new compound represented by the following formula 1 or a salt thereof, which exhibits an excellent effect of promoting the growth of dermal papilla cells to thereby exhibit the effect of promoting hair growth: wherein R is any one selected from the group consisting of 2-methylbutyryl, 3-methylbutyryl, cinnamoyl, 4-pentenoyl, 10-undecenoyl, isobutyl formate, 2,4-dihydroxybenzoyl, geranyl, farnesyl, acryloyl, propanone, 2-pentanone, 1-(4-hydroxyphenyl)ethanone, 1-(2,4-dihydroxyphenyl)ethanone, pentanoic acid, 2-hydroxypropanoic acid, 2-phenylacetic acid, 2-(4-(propanoyl)phenyl)acetic acid, 4-methylbenzoic acid, 4-(4-phenyl)-4-oxobutanoic acid, 2-oxoethyl acetyl, 2-phenoxyacetyl, 2-(benzyloxy)acetyl, 4-methoxybenzoyl, 3,5-dimethylphenol, 6-methoxybenzene-1,4-diol, propenylbenzene, and 4-hydroxycoumarin.

COMPOSITION FOR PROMOTING HAIR GROWTH CONTAINING NOVEL PANTETHEINE DERIVATIVE

Provided is a composition for promoting hair growth, containing, as an active ingredient, a new compound represented by the following formula 1 or a salt thereof, which exhibits an excellent effect of promoting the growth of dermal papilla cells to thereby exhibit the effect of promoting hair growth: wherein R is any one selected from the group consisting of 2-methylbutyryl, 3-methylbutyryl, cinnamoyl, 4-pentenoyl, 10-undecenoyl, isobutyl formate, 2,4-dihydroxybenzoyl, geranyl, farnesyl, acryloyl, propanone, 2-pentanone, 1-(4-hydroxyphenyl)ethanone, 1-(2,4-dihydroxyphenyl)ethanone, pentanoic acid, 2-hydroxypropanoic acid, 2-phenylacetic acid, 2-(4-(propanoyl)phenyl)acetic acid, 4-methylbenzoic acid, 4-(4-phenyl)-4-oxobutanoic acid, 2-oxoethyl acetyl, 2-phenoxyacetyl, 2-(benzyloxy)acetyl, 4-methoxybenzoyl, 3,5-dimethylphenol, 6-methoxybenzene-1,4-diol, propenylbenzene, and 4-hydroxycoumarin.

Composition for promoting hair growth and restoration comprising new derivatives of pantetheine

The present invention relates to a composition for promoting the growth and restoration of hair, comprising a novel compound represented by chemical formula 1 and salt thereof as an active components. In the chemical formula 1, R is any one selected from the group consisting of 2-methylbutyryl, 3-methylbutyryl, cinnamoyl, 4-pentenoyl, 10-undecenoyl, isobutyl formate, 2,4-dihydroxybenzoyl, geranyl, farnesyl, acryloyl, propanone, 2-pentanone, 1-(4-hydroxyphenyl)ethanone, 1-(2,4-dihydroxyphenyl)ethanone, pentanoic acid, 2-hydroxypropanoic acid, 2-phenylacetic acid, 2-(4-(propanoyl)phenyl)acetic acid, 4-methylbenzoic acid,4-(4-phenyl)-4-oxobutanoic acid, 2-oxoethyl acetyl, 2-phenoxyacetyl, 2-(benzyloxy)acetyl, 4-methoxybenzoyl, 3,5-dimethylphenol, 6-methoxybenzene-1,4-diol, propenylbenzene, and 4-hydroxycoumarin.COPYRIGHT KIPO 2017

A widespread bacterial phenazine forms S-conjugates with biogenic thiols and crosslinks proteins

Phenazines are redox-active compounds produced by a range of bacteria, including many pathogens. Endowed with various biological activities, these ubiquitous N-heterocycles are well known for their ability to generate reactive oxygen species by redox cycling. Phenazines may lead to an irreversible depletion of glutathione, but a detailed mechanism has remained elusive. Furthermore, it is not understood why phenazines have so many protein targets and cause protein misfolding as well as their aggregation. Here we report the discovery of unprecedented conjugates (panphenazines A, B) of panthetheine and phenazine-1-carboxylic (PCA) acid from a Kitasatospora sp., which prompted us to investigate their biogenesis. We found that PCA reacts with diverse biogenic thiols under radical-forming conditions, which provides a plausible model for irreversible glutathione depletion. To evaluate the scope of the reaction in cells we designed biotin and rhodamine conjugates for protein labelling and examined their covalent fusion with model proteins (ketosynthase, carbonic anhydrase III, albumin). Our results reveal important, yet overlooked biological roles of phenazines and show for the first time their function in protein conjugation and crosslinking.

An Efficient Chemoenzymatic Synthesis of Coenzyme A and Its Disulfide

We have developed a chemoenzymatic route to coenzyme A (CoASH) and its disulfide that is amenable to gram-scale synthesis using standard laboratory equipment. By synthesizing the symmetrical disulfide of pantetheine (pantethine), we avoided the need to mask the reactive sulfhydryl and also prevented sulfur oxidation byproducts. No chromatography is required in our synthetic route to pantethine, which facilitates scale-up. Furthermore, we discovered that all three enzymes of the CoASH salvage pathway (pantetheine kinase, phosphopantetheine adenyltransferase, and dephospho-coenzyme A kinase) accept the disulfide of the natural substrates and functionalize both ends of the molecules. This yields CoA disulfide as the product of the enzymatic cascade, a much more stable form of the cofactor. Free CoASH can be prepared by in situ S-S reduction.

COMPOSITIONS AND METHODS FOR THE TREATMENT OF INFLAMMATION AND LIPID DISORDERS

The invention relates to the compounds of formula I and formula II or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I or formula II; and methods for treating or preventing inflammation and lipid disorders may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of hypertriglyceridemia, steatohepatitis, cystinosis and inflammatory diseases.

SYNTHESIS OF ACYL-PANTETHEINE DERIVATIVES AND THE USE THEREOF IN THE SYNTHESIS OF ACYL-COENZYME A DERIVATIVES

The present invention relates to a novel synthesis method for acyl-pantetheine derivatives. The present invention further relates to the use of said synthesized acyl-pantetheine derivatives as a starting material in the enzymatic synthesis of acyl-coenzyme A derivatives. According to a first aspect thereof, the present invention provides a method for the synthesis of acyl-pantetheine derivatives, the method including the steps of: a) providing a source of pantetheine; b) providing a source of acyl ester; and c) contacting the source of pantetheine with the source of acyl ester to form the corresponding acyl-pantetheine derivative, having the general formula (I), wherein R is an acyl group.The present invention also provides a method for the synthesis of acyl-coenzyme A derivatives as well as the use of a source of pantetheine and a source of acyl ester in the preparation steps of these two methods.