摘要:

The 24‐hour profile of plasma levels of immunoreactive β‐MSH (IR‐βMSH), ACTH and cortisol was obtained at 15‐min intervals in six normal males in summer and winter. In the radioimmunoassay used, dilution curves of human β‐MSH and human β‐LPH were not parallel. A seasonal variation in basal pituitary‐adrenal secretion, with higher levels in winter than in summer, was demonstrated. A circadian rhythm was found to be significant for ACTH, IR‐βMSH and cortisol in all investigations. Whereas ACTH and cortisol patterns were largely concordant in all studies, there was a significant desynchronization of the circadian rhythm of IR‐βMSH as compared to ACTH in five cases. Eighty‐ three percent of the secretory spikes of cortisol but only 68% of the IR‐βMSH spikes were concomitant with an ACTH spike. Correlations between maximal levels of concomitant spikes were higher during the quiescent period of pituitary‐adrenal secretion (22.00–04.00) for ACTH‐cortisol whereas for ACTH‐ IR‐βMSH, highest correlations were found during the active early morning secretory phase (04.00–10.00). For the three plasma constituents studied, longer apparent half‐lives were found to occur when the basal level before spiking was already elevated, suggesting that ACTH, β‐LPH and cortisol are secreted in bursts superimposed on a continuous basal secretion. Absolute increments of concentration appeared to be relatively independent of the level before spiking. It is suggested that the dissociations between ACTH and IR‐βMSH fluctuations in plasma observ

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1981.tb01962.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Substitution of 9‐D‐Ala‐NH2for 9‐Gly‐NH2in the arginine‐vasopressin molecule (AVP) results in suppression of both pressor and antidiuretic activities, but leaves intact and augmented the ability of the analog to increase plasma levels of Factor VIII (FVIII). This change in the biological spectrum of AVP activities is also present when the N‐terminus of the analog is desaminated and when the 1–6 disulfide bridge is converted to a thioether bridge. The vasopressin receptor (VR) involved in the FVIII mobilization response appears to represent a third category of VR which is distinct from the smooth muscle VR and the antidiuretic VR in terms of conformational requirements for hormone‐receptor triggering. By comparing plasma FVIII levels in mixed venous blood after intravenous and various intra‐arterial injections, evidence was adduced that this third (hematological) category of receptor site (HF‐R) is in the central nervous system (CNS). Donor‐receiver experiments were carried out in anesthetized dogs. The donor animal was given the 9‐D‐Ala‐NH2analog of AVP (dDAlaAVP) by injection into the femoral vein and blood was withdrawn from the internal jugular vein 20 min later; then an injection of 20 ml plasma obtained from this latter sample of donor blood was injected into the femoral vein of a receiver animal. This injection elicited the largest dDAlaAVP‐induced increase in plasma FVIII level yet observed (under all experimental conditions employed to date), strongly suggesting (a) that the brain releases a hitherto unrecognized mobilizing (synthesis‐stimulating and/or releasing) factor for FVIII, (b) that the hematological factor receptor (HF‐R) at which dDAlaAVP acts may be beyond the blood brain barrier and (c) that AVP‐like molecules which act at HF‐R are humoral first messengers in their hematologic function as they are in their actions on smooth muscle and the distal nephron – but at the HF‐R, unlike at the pressor and antidiuretic receptors, these molecules function to effect the release of humoral second messengers which in turn bring about the release and/or increased synthesis of FVIII and plasminogen activator (PA). The 9‐D‐ Ala‐NH2AVP analog should offer advantage over 1‐desamino‐[8‐D‐Arg]‐VP (dDAVP) in the management of bleeding syndromes related to FVIII deficiency because

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1981.tb01963.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

The cyclopentapeptide, ·L·Val1‐L· Pro2‐Gly3‐L· Val4‐Gly5, was synthesized and its conformational characterization was carried out using n.m.r. and theoretical energy calculations. The n.m.r. studies indicated the existence of a cis Val1‐Pro2peptide bond in water and a very strong intramolecular H‐bond between the Val1NH and Gly3C=O groups. This H‐bond forms a β‐turn (type II) placing Val4Gly5residues within the turn. Two minimum energy conformations were derived, one of which agrees very well with the s

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1981.tb01964.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

The primary structures of the four human salivary anionic proline‐rich proteins and an analogous protein from the saliva of a monkey (Macaca arctoides) have been further investigated. These proteins possess the unusual property of inhibiting crystal growth of calcium phosphate salts, and it has been proposed that they play an important role in the mouth, by preventing precipitation of calcium phosphate salts from the supersaturated saliva.The tryptic fragments responsible for this activity have been isolated from all five proteins and their complete amino acid sequences determined and compared. These active fragments have been unequivocally identified as the amino‐terminal segment in all five proteins. The structures of the four human fragments are identical except for the presence of Asn at residue 4 in PRP‐1 and ‐3 instead of Asp found in PRP‐2 and ‐4. Comparison of the 30 residue human fragments with the monkey fragment shows 18 residues to be identical in these peptides, providing that residue 1 of the monkey fragment is aligned with residue 3 of the human proteins.These studies constitute the next step in determining the mechanism of action of these unusual proteins, and in determining their minimum chain length required for inhibito

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1981.tb01965.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Reports concerning anomalous rates of exchange of some amides in oxytocin, alumichrome, and gramicidin S are reexamined through systematic analysis of the exchange data as a function of pH and primary structure. It is shown that such an analysis can provide useful information on secondary structure when the degree of hydrogen bonding to both the NH undergoing exchange and the neighboring carbonyl group are taken into consideration.

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1981.tb01966.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

[7‐(3, 4‐Dehydroproline), 8‐arginine]vasopressin ([Δ3‐Pro7]AVP), an active analog of the naturally occurring neurohypophyseal hormone [8‐arginine]vasopressin (AVP), was studied in D2O at pD 3.3 and 23° by1H n.m.r. spectroscopy, and chemical shifts (SdLs) and some of the coupling constants for the nonlabile protons (1Hs) were determined and compared to those previously reported by us for AVP in D2O at pD 3.8 and 20° (Wyssbrod et al., 7979a, b). Double‐ resonance difference spectroscopy (Gibbons et al., 1975) was used to reveal positions of certain resonances obscured by overlap with resonances of other1Hs.Values of δ of corresponding protons in [Δ3‐Pro7]AVP and AVP are quite similar, and the small differences that are observed can be explained on the basis of (a) magnetic anisotropy from the double bond in the Δ3‐prolyl residue, (b) a slight difference in acidity of the samples in the two studies, or (c) uncertainty in the experimentally determined value of δ. Values of δ for the1Hs in the Δ3‐prolyl and prolyl residues in the two peptides are reported.Our tentative conclusion is that the differences in reported biological activities of [Δ3‐Pro7]AVP and AVP (Botos et al., 1979) are probably not[Δ3‐PRO7, ARG8] VASOPRESSIN related to a perturbation in the conformational state of the backbone, but that they might be explained, in part, by a change in the conformation of the five‐ membered ring of residue 7 and, in part, by π‐π interaction between the 3‐pyrroline ring of the Δ3‐prolyl residue of [Δ3‐Pro7]AVP and the receptor involved in the antidiuretic response but not the receptor involved in the pressor response, in accordance with the suggestion of Walter (1977) that π‐π interactions might, in some cases, b

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1981.tb01967.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

At 400 MHz the1H chemical shifts, peptide NH‐CαH coupling constants (JNα) and peptide hydrogen exchange rates of [Glu4] oxytocin in aqueous solution closely resemble those previously reported for oxytocin under comparable conditions, indicating that both the parent hormone and its analogue have similar conformations in this solvent. The hydrogen exchange data suggest a dynamic equilibrium between conformation(s) in which the peptide NH's of Asn5Cys6are internally hydrogen bonded and conformation(s) in which these hydrogens are bonded to the solvent. [Glu4]oxytocin forms 1:1 complexes with lanthanide metal ions. The diamagnetic La3+complex exhibits values of JNαvery similar to those of the metal free hormone analogue, suggesting that coordination of the metal is accompanied by minimal perturbation of the peptide backbone. Specific average proton‐metal distances estimated from Gd3+induced paramagnetic relaxation effects indicate that the metal is probably coordinated to the Glu4carboxyl group and the sidechain carbonyl of Asn5. Limiting shifts induced by binding of paramagnetic Yb3+are also re

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1981.tb01968.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

The neurohypophyseal hormones of three species of Australian marsupials belonging to the family Macropodidae (Macropus rufus, Macropus giganteus, Macropus robustus). have been investigated. In these species three active peptides have been disclosed, one with oxytocic activity and two with pressor activity. The three hormones are present in all the individual glands which have been examined. Purification has been undertaken by ion‐exchange chromatography and paper chromatoelectrophoresis. The more abundant of the pressor hormones (about 80% of the total pressor activity) has been identified as lysine‐vasopressin by its biological properties, its chromatographic behaviour and its amino acid composition. The second pressor principle, more basic, has not yet been chemically characterized but its pharmacological properties and its chromatographic behaviour suggest that it is closely related or identical to arginine‐vasopressin. Dimorphism of vasopressins seems peculiar to Metatheria since it has not been observed in Protheria and very rarely in Eut

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1981.tb01969.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

The syntheses of five partial retro‐inverso luteinizing hormone‐releasing hormone (LH‐RH)analogs, [g‐Tyr5, m‐Gly6]LH‐RH, [g‐Tyr5‐r‐Gly6, R,S‐m‐Leu7]LH‐RH, [g‐p‐Glu1, m‐His2]LH‐RH, [g‐p‐Glu1‐r‐D‐His‐R,S‐m‐Trp3]LH‐RH, and [g‐Pro9‐ propionyl‐des‐Gly10]LH‐RH, have been accomplished by solution methods. The choice of sequence to be reversed was based on suggested biodegradation mechanisms of LH‐RH. A (gem)‐diamino alkylidene residue, which was produced via Curtius rearrangement of a peptide segment, and a 2‐substituted malonyl residue mark the initia

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1981.tb01970.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Pure milk‐clotting protease (MCP‐76) is isolated by isotachophoresis at pH 5.0. The native molecule has only one protein chain. It is a metaloenzyme containing zinc. The pure MCP‐76 has a molecular weight of 33 000 (± 1500) and by diphenyl‐indenonyl‐isothiocyanate method showed arginine as N‐termina

ISSN:0367-8377    

DOI:10.1111/j.1399-3011.1981.tb01971.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY