Angiotensin-converting enzyme inhibitors: importance of the amide carbonyl of mercaptoacyl amino acids for hydrogen bonding to the enzyme

Condon, Michael E.; Petrillo, Edward W.; Ryono, Denis E.; Reid, Joyce A.; Neubeck, Richard; Puar, Mohindar S.; Heikes, James E.; Sabo, Emily F.; Losee, Kathryn

doi:10.1021/jm00345a011

Cited by 49 publications

(27 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These compounds can be thought of as partial analogues of the inhibitor glycyl-L-phenylalanine, IC50 = 630/M , with the peptide bond replaced by an ethylene bridge. Replacement of the peptide bond by an ethylene bridge usually causes a large decrease in inhibitory potency (Condon et al, 1982).…”

Section: Discussionmentioning

confidence: 99%

Inhibitors of angiotensin-converting enzyme containing a tetrahedral arsenic atom

Galardy¹,

Kortylewicz²

1985

Biochemical Journal

View full text Add to dashboard Cite

A series of tetrahedral oxo acids of Group VA and VIA elements and of silicon and boron were examined as inhibitors of angiotensin-converting enzyme. Arsenate is a competitive inhibitor with a Ki of 27 +/- 1 mM, at least 10-fold more potent than phosphate. Dimethylarsinate is a competitive inhibitor with a Ki of 70 +/- 9 mM, 2-fold more potent than dimethylphosphinate. Oxo acids of boron, silicon, antimony, sulphur and selenium are not inhibitors. On the basis of these results and the strong inhibition of this zinc metallopeptidase by substrate analogues containing a tetrahedral phosphorus atom, two substrate analogues containing a tetrahedral arsenic atom were prepared. 2-Arsonoacetyl-L-proline is a competitive inhibitor with a Ki of 18 +/- 7 mM, more than 2000-fold weaker than that of its phosphorus analogue 2-phosphonoacetyl-L-proline. 4-Arsono-2-benzylbutanoic acid is a mixed inhibitor with a Ki of 0.5 +/- 0.2 mM, indistinguishable in potency from its phosphorus analogue 2-benzyl-4-phosphonobutanoic acid.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibitors of angiotensin-converting enzyme containing a tetrahedral arsenic atom

Galardy¹,

Kortylewicz²

1985

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…The absorbance is proportional to the H 2 O 2 level, which is decreased by catalase as it degrades the H 2 O 2 . Values were expressed in μmol H 2 O 2 /min/mg 46.…”

mentioning

confidence: 99%

Bergapten Attenuates Nitroglycerin-Induced Migraine Headaches through Inhibition of Oxidative Stress and Inflammatory Mediators

Latif

Khan

Haque

et al. 2021

ACS Chem. Neurosci.

View full text Add to dashboard Cite

The present study intended to examine the effect of bergapten and possible mechanisms involved in the treatment of migraine-associated symptoms in the rat model. Five doses of nitroglycerin (10 mg/kg) were injected intraperitoneal to induce migraine headaches in rats with a one-day break between each dose. Treatment groups received nitroglycerin followed after 1 day by bergapten (50 or 100 mg/kg), saline (10 mL/kg), or sumatriptan (50 mg/kg) once daily for 10 days. Behavioral observations were analyzed 2 h after nitroglycerin injections and 1 h 40 min after treatment. The animals were sacrificed 24 h after the last treatment dose. Samples of trigeminal nucleus caudalis (TNC) and cerebral cortex were collected and analyzed for antioxidant activity and expression of inflammatory markers by immunohistochemistry and enzyme-linked immunosorbent assay. Our findings revealed that bergapten notably decreases headache by altering mechanical allodynia, thermal allodynia, light phobicity, and the number of head-scratching incidence in rats. In the cortex and TNC regions, antioxidant factors were restored, and lipid peroxidation was significantly reduced. Furthermore, bergapten decreased the expression of inflammatory markers, such as nuclear factor kappa B (NF-Kb) and tumor necrosis factor-alpha (TNF-α), as evidenced by immunohistochemistry and ELISA. These results suggest that bergapten exhibits headache-relieving activity, possibly mediated through antioxidant and anti-inflammatory pathways.

show abstract

“…Preliminary experiments, data not shown, revealed that the immediate attachment of vinyl dimethylazlactone at multi thiol‐functional PO X copolymers through radical mediated as well as Michael addition‐based thiol–ene reaction led to cross‐linking of the individual dissolved polymer chains, which was to be expected since attached azlactone rings can be easily opened by remaining thiols of the polymer side chains. Hence, a new mercaptoacyl amino acid, N ‐(3‐mercapto‐1‐oxopropyl)‐2‐methyl‐alanine (MOMA), based on the non‐proteinogenic amino acid 2‐aminoisobutyric acid was synthesized adapted from Condon et al to overcome this problem. The synthesis is a two‐step approach, in the first step, the amine group of the amino acid is transformed into an amide by addition of 3‐bromopropionyl chloride and a thioester is introduced through the addition of thiobenzoic acid in a slightly alkaline environment.…”

Section: Resultsmentioning

confidence: 99%

“…The synthesis of MOMA is a two‐step synthesis adopted from Condon et al to produce mercaptoacyl amino acids. The first step is the synthesis of N ‐[3‐(benzoylthio)‐1‐oxopropyl]‐2‐methylalanine, which is deprotected in the second step to reveal the free thiol.…”

Section: Methodsmentioning

confidence: 99%

In Situ Polymer Analogue Generation of Azlactone Functions at Poly(oxazoline)s for Peptide Conjugation

Liebscher

Teßmar

Groll

2019

Macro Chemistry & Physics

View full text Add to dashboard Cite

The most prominent polymer for many biomedical applications is presently poly(ethylene glycol) (PEG), which can ameliorate the stability of the peptide structure regarding harsh environmental conditions. [3,5,6] However, other water-soluble polymers that offer multiple conjugation sites through multiple side chain functionalities can be interesting alternatives to PEG, which only offers αor ω-end functionalization. One of those polymers are poly(2-alkyl-2-oxazoline)s (PO X), which have already been explored for peptide-polymer conjugation by several researchers. [7,8] For example, Luxenhofer et al. attached a cyclic RGD peptide using copper mediated click-chemistry [9,10] and Schmitz et al. [11] attached thioester functional peptides to a multifunctional cysteine PO X copolymer. PO X is generally synthesized via cationic ring opening polymerization (CROP) and through a vast variety of monomers, different functional side chains can be easily incorporated into the polymer using appropriate copoly merization schemes. [12] Another interesting functionality for such polymers is the electrophilic azlactone, which is basically a "masked" amino acid [13] and readily reacts with amines, thiols, and hydroxyls [14] without additional activation and the formation of any by-products. Based on these advantages, it could be a pro mising alternative to the commonly used N-hydroxysuccinimide active esters used in many conjugation reactions. [15-17] Azlactones have already been used in peptide ligation as they offer the opportunity to integrate chiral amino acids through stereoselective alkylation with subsequent ligation. [18] In polymer chemistry, 2-vinyl-4,4-dimethyl azlactone (VDMA) has been so far mainly polymerized by free radical polymerization using methacrylic acid as co-monomer, by atom transfer radical polymerization [19] to receive pure PVDMA or by reversible addition-fragmentation chain transfer (RAFT) polymerization with N-isopropyl acrylamide and N,N-dimethylacrylamide. [20] Surface anchored PVDMA brushes have also been used for protein immobilization, for example, RNase A, where the activity of the immobilized protein was close to the free enzyme. [21] Vinyl-functional azlactones were also applied for macromonomer functionalization, for example, amino group bearing gelatin was functionalized with 2-isopropenyl-4,4-dimethylazlactone at room temperature making it available for the formation of hydrogels via radical cross-linking, which was used to support in vitro cell growth. [22] Copolymers of poly(ethylene glycol methyl ether methacrylate-ran-vinyl azlactone-ran-glycidyl methacrylate) The physical and chemical stability of peptides for biomedical applications can be greatly enhanced through the conjugation of polymers. A well-known but rather underemployed selective coupling functionality is the azlactone group, which readily reacts with a number of different nucleophiles without the need for activation and the formation of any by-products. For example, azlactone functional polymers are used to react with peptides...

show abstract

Angiotensin-converting enzyme inhibitors: importance of the amide carbonyl of mercaptoacyl amino acids for hydrogen bonding to the enzyme

Cited by 49 publications

References 0 publications

Inhibitors of angiotensin-converting enzyme containing a tetrahedral arsenic atom

Inhibitors of angiotensin-converting enzyme containing a tetrahedral arsenic atom

Bergapten Attenuates Nitroglycerin-Induced Migraine Headaches through Inhibition of Oxidative Stress and Inflammatory Mediators

In Situ Polymer Analogue Generation of Azlactone Functions at Poly(oxazoline)s for Peptide Conjugation

Contact Info

Product

Resources

About