摘要:

The biosynthesis of neuro and hormonal peptides is in a state of rapid progress. The development of protein microsequencing is making it possible to characterize more and more new important molecules with nanomolar quantities, while the DNA structural studies favor the sequencing of the precursors of all these new peptides. These precursors are often polyproteins containing more than one active end‐product. Their maturation processes are following a highly similar pattern with cleavage of the precursors at sites characterized by the presence of pairs of basic amino acid as noted in 1967–68 for the LPH and the pro‐insulin models. This now constitutes a general concept which has good chances to be applicable to all the exciting neuro and hormonal peptides recently identified or yet to be disco

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1984.tb02728.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

The attachment of Fmoc‐amino acids ontop‐alkoxybenzyl alcohol resinsviaDCC‐DMAP coupling suffers from two different problems: formation of dimers and racemization. The use ofN,N‐dimethylformamide dineopentyl acetal for the preparation of Fmoc‐aminoacyloxybenzyl handles is the basis of a safe and efficient anchoring method that avoids both

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1984.tb02729.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Intraventricular injection of β‐endorphin (3, 7, 10 and 30 nmol/kg) into the third ventricular of pentobarbital‐anaesthetized male Sprague‐Dawley rats resulted in a dose‐dependent increase in mean arterial pressure (MAP) while injection of the same volume of 0.9% NaC1 solution did not cause significant changes in MAP. Naloxone, which did not produce any significant change in MAP, antagonized the vasopressor effect of β‐endorphin, indicating that the response is mediated via the naloxone sensitive opiate receptors. Rats acclimated to cold (5°) for 3 weeks showed a potentiated and prolonged increase in MAP following β‐endorphin injection, indicating an increased responsiveness to the peptide. This increased responsiveness in the cardiovascular system is probably of adaptive value in cold acclimation. Naloxone itself did not alter MAP either, but abolished the cardiovascular response to β‐endorphin completely in cold acclimated rats, indicating an increased effectiveness in its antagonistic effect following cold a

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1984.tb02730.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

The conformational behavior of the activeC‐terminal heptapeptide of neurotensin (NT), Pro‐Arg‐Arg‐Pro‐Tyr‐Ile‐LeuOH, or NT{7–13}, was investigated using empirical energy calculations. A sequential approach was used to display the specific contribution of each residue to induce stable conformations of the whole heptapeptide. The most stable conformations include numerous conformations of various types in a rather limited energy range. There is no preferential conformation contrary to the activeC‐terminal pentapeptide. These structures may coexist in the biolo

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1984.tb02731.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Dynorphin‐(1–13) (Dyn‐(1–13)) and its analogs substituted by single introduction of Ala in positions 1–11 were synthesized by the solid‐phase method and purified by high pressure liquid chromatography. Relative potencies of the synthetic compounds were determined by their ability to inhibit electrically‐evoked contractions of the guinea pig ileum (GPI) and of the mouse vas deferens (MVD) and to compete with [3H]‐etorphine for opiate receptors in rat brain homogenates. Introduction of Ala in positions 1 and 4 of Dyn‐(1–13) provoked most important decreases in the activity of the molecule in the three assays (relative potency of 0.2% or less). Substitution of Ala in positions 2 or 5, but not 3, also severely decreased the potency of the peptide in the smooth muscle preparations (0.6–5.0% activity). However, the opiate receptor binding assay was less sensitive to the replacement of residue in position 2 (20% activity) than that in positions 3 or 5 (12% and 6% relative potencies, respectively). In the GPI assay and the opiate binding test, the other substitutions which greatly lowered the potency of the molecule were seen in positions 6, 7, 9 and 11, four basic residues. Among these, Arg6and Arg7were demonstrated to be the most important in the three biological tests. Finally, the replacement of Ile8by Ala increased the relative potency of Dyn‐(1–13) up to 191% and 900% in the MVD and the opiate bi

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1984.tb02732.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

The preparation of the 4‐sulfobenzyl esters of 18 amino acid derivatives is described. This carboxyl protecting group was introduced according to Hubbuchet al.(1980). The caesium or dicyclohexylammonium salts ofN‐terminal protected amino acids were reacted with 4‐(bromomethyl)benzenesulfonate (1). AfterN‐terminal deblocking, the amino acid‐4‐sulfobenzyl esters were isolated as zwitterions. The protecting group was removable by catalytic hydrogenation and by saponification. The 4‐sulfobenzyl esters could be easily converted to amides and hydrazides. They were stable to 2 M hydrogen bromide in acetic acid as well as to a 10‐fold excess of trifluoromethane sulfonic acid in trifluoro‐acetic acid. The behaviours of+H2‐Gly‐Phe‐Leu‐OBzl‐SO‐3and the corresponding methyl, benzyl and 4‐nitrobenzyl esters were co

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1984.tb02733.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Amino acid 4‐sulfobenzyl esters were employed for the synthesis of peptides in solution. They significantly increase the hydrophilicity of protected intermediates as shown by analytical reversed‐phase high performance liquid chromatography and counter‐current distribution. General methods for working up are described which permit simple and standardized isolations of products. The use of several coupling methods was demonstrated in the synthesis of Z‐Val‐Gly‐OBzl‐SO3NH4. Ion‐exchange chromatography was introduced as a selective purification procedure for protected peptide 4‐sulfobenzyl esters. A step‐wise synthesis of [Leu5]‐enkephalin was performed, starting from leucine 4‐sulfobenzyl ester. Removal ofN‐terminal protecting groups produced zwitterionic peptide 4‐sulfobenzyl esters. These were readily purified by crystallization from slightly acidic media; no further purification was necessary. The biologically fully active pentapeptide Tyr‐Gly‐Gly‐Phe‐Leu was ob

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1984.tb02734.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

A method for studying denaturation of an enzyme by n.m.r. measurements of its specific inhibitor is reported and discussed for the case of lysozyme andN‐acetyl glucose amine. It was shown that in the presence of bound inhibitor molecules, the enzyme is more resistant to the denaturant agent as compared to the free enzym

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1984.tb02735.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Self‐associated species of the protectedC‐terminal tetrapeptide segment of porcine vasoactive intestinal peptide and related short sequences in methylene chloride have been disrupted by adding increasing amounts of dimethylsulphoxide. This structural transition has been monitored following the disappearance of the amide I carbonyl stretching band assigned to strongly intermolecularly hydrogen‐bonded molecules (1655–1633 cm‐1) in the infrared absorption spectra. A scale for the propensity of the various peptides to aggregate has been established. Substitution of the asparagine residue by a β‐tert.‐butylaspartic acid residue in the tripeptide drastically reduces the extent of self‐association. The increasing tendency to aggregate shown by these peptides is paralleled by a decrease in their solubility. The impact of these results on the strategy of synthesis of porcine vasoactive intestinal peptide is

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1984.tb02736.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Human [10‐asparagine‐B] insulin ([Asn10‐B] insulin), an analogue which differs from the parent molecule in that the histidine residue at position 10 of the B chain (B10) is replaced by asparagine, has been synthesized and isolated in purified form.In vitrobiological assays indicated a potency ofca.35% compared to insulin. We have previously shown that the replacement of histidine at position B10by lysine resulted in an analogue displayingca.15% of the biological activity of natural hormone, while the substitution of leucine in this position produced a molecule exhibitingca.45% potency inin vivoassays. The data indicate that molecular size of the amino acid residue at position B10may be important in the maintenance of a structure commensurate with high biological activity. Polarity at this position appears to be rather unimportant while a strongly basic group appears to be delete

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1984.tb02737.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY