An Advantageous Method for the Rapid Removal of Hydrogenolysable Protecting Groups under Ambient Conditions; Synthesis of Leucine-enkephalin

Anwer, Mohmed K.; Spatola, Arno F.

doi:10.1055/s-1980-29275

Cited by 173 publications

(61 citation statements)

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Section: Methodsmentioning

confidence: 99%

“…All peptide couplings were carried out using BOP as the activating agent and one equivalent of each protected amino acid as described (13). Final removal of protection from the side chains was achieved by catalytic transfer hydrogenolysis using ammonium formate as a hydrogen donor (14).The purity of all synthesized compounds was checked by TLC on silica gel plates (Merck). The following solvent systems were used: ethyl acetate (solvent system A), chloroform/methanol/acetic acid (95:5:3) (solvent system B), 1-butanol/acetic acid/water (4:1:1) (solvent system C), 1-butanol/pyridine/acetic acid/water (30:20:26:4) (solvent system D).…”

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confidence: 99%

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Synthesis of peptides related to the prosegment of mouse submaxillary gland renin precursor: an approach to renin inhibitors.

Evin¹,

Devin²,

Castro³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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The complete sequence of the structural gene coding for mouse submaxillary gland renin was recently reported and the amino acid sequence of preprorenin was deduced. This sequence includes a 45-amino acid peptide that corresponds to the prosegment of the renin precursor. To investigate whether peptides related to the renin prosegment are able to inhibit renin activity, we have synthesized four peptides having the following structures: Arg-Ile-Pro-OMe, butyloxycarbonyl(Boc)-Leu-Lys-Lys-Met-Pro-OMe, Boc-Arg-Ile-ProLeu-Lys-Lys-Met-Pro-OMe, and Boc-Glu-Arg-Ile-Pro-LeuLys-Lys-Met-Pro-OMe (corresponding to amino acids 12-14, L-19, 12-19, and 11-19, respectively, of the renin prosegment). All four peptides were found to inhibit the activity of pure mouse submaxillary renin on a porcine synthetic tetradecapeptide in vitro, and the most potent inhibitors exhibited ICso values in the micromolar range. Enzymatic kinetic studies carried out using peptide 15-19 showed an uncompetitive or a mixed type of inhibition with a Ki value of 2.3 x 10-6 M at 37°C in 0.5 M citrate/phosphate buffer (pH 6.0).Renin plays an important role in the regulation of blood pressure and electrolyte metabolism (1). It is a very specific aspartyl protease that reacts with its substrate angiotensinogen to release angiotensin I. Mouse submaxillary gland renin has physicochemical, enzymatic, and immunological properties similar to those of the renal enzyme (2, 3). The complete sequence of the structural gene coding for mouse submaxillary renin has been reported by Panthier et al., and the amino acid sequence of preprorenin was deduced (4). A hypothesis for renin processing consisting of a three-step mechanism has been proposed (4): (i) the removal of a signal peptide leading to prorenin, (ii) the cleavage of an NH2-terminal activation peptide later referred to as the prosegment, (iii) the splitting of the renin molecule into two chains linked by a disulfide bond to give the mature active enzyme. The exact length of the signal peptide could not be determined, but by analogy with the signal peptides of other proteins, an 18-amino acid peptide (-18 to -1) was proposed by Panthier et al. (4). Consequently, the prosegment of prorenin was proposed to be a 45-amino acid peptide (1-45).Other aspartyl proteases, such as pepsin and chymosin, are processed from an inactive precursor with the release of a prosegment to give active enzymes (5-7). Furthermore, the recent elucidation of the structural gene coding for human pepsin has shown that the pepsin precursor also contains a 15-amino acid signal peptide and a 47-amino acid activation segment (8). In all cases the prosegments are located at the NH2 terminus and have a length comparable to that of the putative renin prosegment. A notable homology has been found in the prosegment sequences of the renin precursor and of pepsinogen, particularly in the NH2-terminal region (Fig. 1).Interestingly, the enzymatic activities of bovine and porcine pepsins are inhibited by peptide fragments from the prosegments of ...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Synthesis of peptides related to the prosegment of mouse submaxillary gland renin precursor: an approach to renin inhibitors.

Evin¹,

Devin²,

Castro³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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“…( I ) Catalytic transfer hydrogenation using ammonium formate in methanol and 10% Pd/C (16 For personal use only.…”

Section: Synthesis Of Phosphonolactone 12mentioning

confidence: 99%

γ-Phosphono-γ-lactones. The use of allyl esters as easily removable phosphonate protecting groups

Kamber¹,

Just²

1985

Can. J. Chem.

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“…[42][43][44]. In situ hydrogen formation in the reaction mixture increases the gas-liquid-solid phase interaction, helps to control the stoichiometry of the reagents, and, most importantly, helps to avoid the risk of fire and explosion associated with using hydrogen gas (especially when dealing with larger scale synthesis).…”

Section: Resultsmentioning

confidence: 99%

“…In situ hydrogen formation in the reaction mixture increases the gas-liquid-solid phase interaction, helps to control the stoichiometry of the reagents, and, most importantly, helps to avoid the risk of fire and explosion associated with using hydrogen gas (especially when dealing with larger scale synthesis). We used ammonium formate, which shows more advantages in comparison to the others [43,[45][46][47][48][49], as a hydrogen donor. Ammonium formate acts as a hydrogen equivalent that may be presented either in the adsorbed form on palladium or in the palladium hydride form [49].…”

Section: Resultsmentioning

confidence: 99%

Synthesis of N-Hydroxypyrazin-2(1H)-ones via Selective O-Debenzylation of 1-Benzyloxypyrazin-2(1H)-ones Using Flow Methodology

Hung¹,

Borggraeve²

2015

J Flow Chem

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An Advantageous Method for the Rapid Removal of Hydrogenolysable Protecting Groups under Ambient Conditions; Synthesis of Leucine-enkephalin

Cited by 173 publications

References 0 publications

Synthesis of peptides related to the prosegment of mouse submaxillary gland renin precursor: an approach to renin inhibitors.

Synthesis of peptides related to the prosegment of mouse submaxillary gland renin precursor: an approach to renin inhibitors.

γ-Phosphono-γ-lactones. The use of allyl esters as easily removable phosphonate protecting groups

Synthesis of N-Hydroxypyrazin-2(1H)-ones via Selective O-Debenzylation of 1-Benzyloxypyrazin-2(1H)-ones Using Flow Methodology

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