Synthetic peptides related to eledoisin. Physalaemin-like peptides

Bernardi, L.; Bosisio, G.; Chillemi, Francesco; de, G.; Castiglione, Roberto; Erspamer, V.; Goffredo, O.

doi:10.1007/bf01897751

Cited by 24 publications

(8 citation statements)

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“…In addition, it should be noted for future studies that the N-terminal-shortened octapeptides from tachykinins with a variety of carbonyl-protected amino acids at the N-terminal were the most effective for biological activity (Bergmann et al, 1974;Lubke et al, 1965). The C-terminal hexapeptide caused salivation but with significantly less activity consistent with some reports on the C-terminal hepta-or hexa-peptides of SP for salivation and of physalaemin for other biological actions (Bernardi et al, 1966;Leeman et al, 1977;Hanley et al, 1980;Togari et al, 1980). The C-terminal pentapeptide or smaller fragments of physalaemin did not cause any salivation, in accord with a few reports (Bernardi et al, 1966;Hanley et al, 1980;Takano et al, 1985).…”

Section: Structure-sialogogic Activity Relationships In Naturally Occsupporting

confidence: 82%

“…Since von Euler and Gaddum (1931) first discovered substance P (SP) present in alcoholic extracts of equine brain and intestine, biophysiological roles of SP have been studied, including its ability to act as a sialogogue (Leeman and Hammerschlag, 1967;Lembeck et al, 1968b). Many tachykinins analogous to SP have been discovered, such as eledoisin (Erspamer, 1949;Erspamer and Anastasi, 1962), physalaemin (Erspamer et al, 1964;Bernardi et al, 1966), eledoisin-related peptide (Sakakibara and Fujino, 1966), kassinin (Anastasi et al, 1977), substance K (neurokinin A or neuromedin L; Kimura et al, 1983;Nawa et al, 1983), and neurokinin B (neuromedin K; Kangawa et al, 1983). Until recently SP was regarded as the only tachykinin occurring in the vertebrate central nervous system and intestine.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, there are several reports on the structure-activity studies of these tachykinins on intestinal smooth muscle contraction and hypotension (eg, Sandberg and Iversen, 1982). Relative biological activities among salivation, smooth muscle contraction and hypotension may vary conspicuously according to the different test objects, even when the same tachykinin was used 181 (Bernardi et al, 1966;de Caro, 1966;Erspamer et al, 1980). Therefore, the structure-activity relationships of such tachykinins for salivation requires more clarification.…”

Section: Introductionmentioning

confidence: 99%

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Structure‐activity relationships of sialogogic heptapeptides analogous to physalaemin

Gao

2000

Oral Diseases

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OBJECTIVES: The rationale behind this study was to determine in detail which amino acids in physalaemin are crucial to its sialogogue activity, with a view of synthesizing new sialogogues which might be of use in the treatment of dry mouth. METHODS: With the progressive elimination of amino acids, one by one, from the C‐ and N‐terminal regions, 126 heptapeptides were newly synthesized by the multi‐pin peptide method, for comparison with 11 naturally occurring tachykinins. RESULTS: The C‐terminal amide in position 11 was essential for salivation, but not the pyrolidine group or the N‐terminal amino acid residues in positions 1 to 4. In 18 heptapeptides in which M in position 11 (M11) was replaced by another amino acid, one by one, none caused salivation. In 18 heptapeptides, in which L10 or G9 was replaced, three peptides caused salivation but none had significantly increased secretory activities. In 18 hepta‐peptides in which Y8 was replaced, four caused salivation but only one (I) had significantly increased secretory activity. In 18 heptapeptides in which F7 was replaced, only Y caused salivation but with significantly reduced secretory activity. In contrast, in 18 heptapeptides in which K6 and N5 were replaced, most caused salivation and some of them had significantly increased secretory activities. CONCLUSIONS: It is concluded that the sequence FYGLM‐NH2 conserved in the C‐terminal region of phys‐alaemin is optimal, that amides in position 11 and F7 are very important for salivation, but that K6 and N5 can be replaced by some other amino acids, resulting in increased secretory activities.

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Section: Structure-sialogogic Activity Relationships In Naturally Occsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Structure‐activity relationships of sialogogic heptapeptides analogous to physalaemin

Gao

2000

Oral Diseases

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“…Eledoisin is slightly less active than substance P on the guinea-pig ileum but is only 17% as potent as substance P in eliciting vasodilatation (Rury, 1976). However, for physalaemin, the hypotensive activity has been shown to be 4-5 times and the spasmogenic activity on the guinea-pig ileum approximately twice that of eledoisin (Bernardi et al, 1966). Thus, relative to eledoisin, potencies of physalaemin and substance P appear to be similar in both vascular and intestinal tissues.…”

Section: Structure-activity Relationships Eor Substance Pmentioning

confidence: 96%

“…Since the pentapeptides have appreciable activity and the highly active C-terminal hexapeptides of eledoisin and physalaemin have different N-terminal amino acids (alanine and lysine respectively), it was not surprising that substitution with different amino acids did not produce marked changes in activity. However, hexapeptides with N-terminal basic amino acids (lysine, ornithine, arginine) were approximately five times more potent than those with neutral amino acid (serine, alanine) substitutions (Rernardi, 1966;Bernardi et al, 1966). This high activity does not appear to be due to the presence of basic w groups since their acetylation does not reduce the activity (Rernardi et al, 1964).…”

Section: Structure-activity Relationships Eor Substance Pmentioning

confidence: 99%

Substance P: Its Pharmacology and Physiological Roles

Bury

Mashford

1977

Aust J Exp Biol Med

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Summary. The recent identification and synthesis of the endecapeptide substance P has renewed interest in this naturally occurring compound. The original substance P of Euler and Gadduni was a mixture of biologically active substances, some of which were peptides. The peptide component was responsible for gut-contracting, hypotensive and sialogogic properties attributed to substance P. For almost 40 years following its discovery, substance P resisted isolation and purification. Even the most highly active preparations were heterogeneous and there was a divergence of results from experiments using preparations which were partially purified by different techniques. Nevertheless, much of the early work on the distribution and pharmacology of crude substance P has been confirmed using the synthetic endecapeptide and has stimulated research towards the elucidation of a possible functional role for substance P. Most proposed functions have been highly speculative but, at present, evidence is accumulating in support of a physiological role for substance P as a neurotransniitter in sensory pathways. DISCOVERY, PURIFICATION AND ISOLATION OF SUBSTANCE P.While investigating the distribution of acetylcholine in various tissues in 1931, Euler and Caddum detected the presence of a substance in alcoholic extracts of equine brain and intestine which stimulated contraction of isolated rabbit intestine. On intravenous administration to anaesthetized rabbits, this preparation briefly lowered the blood pressure. These effects differed qualitatively from those of acetylcholine and, in addition, were not inhibited by atropine. The active moiety found in the dried extracts was given the working designation "preparation P" and was shown to differ in its chemical and biological properties from other smooth muscle stimulating substances then known, viz. histamine and the adenine nucleotides. The new active factor, provisionally named substance P (Caddum and Schild, 1934), was first recognised as a protein-like material by Euler (1936a).

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Synthesis of [2‐p‐Fluorophenylalanine]oxytocin and its Desamino Analogue Using the S‐Acetamidomethyl Protecting Group

Marbach¹,

Rudinger²

1974

Helvetica Chimica Acta

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Summary.[2-p-Fluorophenylalanine]oxytocin (la), desamino-[2-#-fluorophenylalanine]oxytocin (lb), and desamino-oxytocin (2) have been synthesised via intermediates containing S-acetamidomethyl-cysteine. The protected linear peptides were built up using both stepwise and fragment-condensation procedures, and the S-protecting groups were removed by iodine with simultaneous formation of the disulfide bridge. The uterotonic activities i n vitvo of the analogues have been determined. The close similarity of the lgF-NMR. spectra indicates that the p-fluorobenzyl side chain is freely exposed to the solvent in the disulfide-bridged hormone analogues as well as in their S-protected, acyclic precursors.$-Fluorophenylalanine analogues of biologically active peptides have been prepared for the study of structure-activity relationships From the Doctoral Dissertation to be submitted by P . Marbach. I n addition to the standard abbreviations for amino acids and protecting groups [14], the following are used: Phe(F) forp-fluorophenylalanine,PMp for 3-mercaptopropionyl, and Spy for 2-pyridylthio ; further, DCCI is used for dicyclohexylcarbodiimide, DCHA for dicyclohexylamine, DMF for dimethylformamide, HOBt for 1-hydroxybenzotriazole, NMM for N-methylmorpholine, and TMG for N, N, N', N'-tetramethylguanidine. All amino acids (except glycine) are of the L configuration unless otherwise stated. The naming of analogues accords with current convention [U],

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Synthetic peptides related to eledoisin. Physalaemin-like peptides

Cited by 24 publications

References 0 publications

Structure‐activity relationships of sialogogic heptapeptides analogous to physalaemin

Structure‐activity relationships of sialogogic heptapeptides analogous to physalaemin

Substance P: Its Pharmacology and Physiological Roles

Synthesis of [2‐p‐Fluorophenylalanine]oxytocin and its Desamino Analogue Using the S‐Acetamidomethyl Protecting Group

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