Tryptophyllins & additional amphibian peptides

 

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TRYPTOPHYLLINS (TPHs)

This name has been suggested to indicate a non homogeneous family of tryptophan-containing tetra-, penta-, hepta-, and trideca- peptides isolated from methanol extracts of Phyllomedusa rohdei skin. They generally have in common a Trp residue at position 2 from the C-terminus and one or two Pro residues, at positions 2 (and 3) from the N-terminus (with the exception of TPH - 13).

Tryptophyllins represent the first example of frog peptides identified not by bioassay, but simply by colour reactions on paperchromatograms.

Their activity remains to be established.

Bioassay on a number of isolated and in situ smooth muscle preparations and on systemic blood pressure, gave negative results. However, in preliminary experiments, which await confirmation, the penta-tryptophyllins showed some effects on gastric emptying in the rat (by intracerebroventricular injection) and, surprisingly, on protein synthesis in rat liver, following subcutaneous injection. Both liver protein synthesis and body weight have been reported to increase after their administration in domestic fowl (including turkeys). The same promoting activity on protein synthesis was displayed also by TPH 7 peptides.

An antiserum against [Met5]TPH 5 was raised in the rabbit. With this antiserum a population of cells was immunostained in the rat, rabbit and frog anterior pituitary.

Tryptophyllins do not seem to be peculiar to Phyllomedusa skin. In fact, tryptophan-containing peptides showing, on paperchromatograms, colour reactions and Rf values very similar to those of the tryptophyllins, occur in methanol extracts of the skin of other hylid frogs of Central and South America.

 

Name

Peptide primary structure

TPH 4

pGlu-Pro-Trp-Met-NH2

pGlu-Pro-Trp-Val-NH2

Phe-ProTrp-Leu-NH2

pGlu-Pro-Trp-Met-OH

pGlu-Ala-Trp-Met-OH

Phe-Pro-Pro-Trp-OH

TPH 5

Phe-Pro-Pro-Trp-Met-NH2

Phe-Pro-Pro-Trp-Val-NH2

Phe-Pro-Pro-Trp-Leu-NH2

Phe-Pro-Pro-TrpLeu-OH

TPH 7

Val-Pro-Pro-Leu-Gly-Trp-Met-OH

Lys-Pro-Hyp-Ser-Trp-Ile-Pro-NH2  (basic tryptophyllin from Phyllomedusa rohdei )

Lys-Pro-Hyp-Ala-Trp-Val-Pro-NH2 (PdT-1 from Pachymedusa dacnicolor )

TPH 13

pGlu-Glu-Lys-Pro-Trp-Pro-Pro-Pro-Ile-Tyr-Pro-Met-O H

References:

"Phyllomedusa Skin: A Huge Factory and Store-House of a Varietry of Active Peptides" by V. Erspamer, P. Melchiorri, G. Falconieri Erspamer, P.C. Montecucchi and R. de Castiglione (1985), Peptides 6, 7-12

"Isolation and primary structure determination of amphibian skin tryptophyllins" by P.C. Montecucchi (1985), Peptides 6, 187 - 195

"Tryptophyllin-like immunoreactivity in rat adenohypophysis" by T. Renda, L. D'Este, R. Buffa, L. Usellini, C. Capella and S. Campo (1985), in: Peptides 6, 197 - 202

"Peptidi come promotori di crescita" by K. Kaemmerer, J. Fink and M. Kietzmann (1985) Riv. Zool. Veter. 13, 3-12

"The application of mass spectrometry to the study of evolutionary trends in amphibians" by Simon T. Steinborner, P.A. Wabnitz,  John H. Bowie, Michael J. Tyler (1996) , Rapid Commun. Mass Spectrom. 10 (1), 92  (The primary structures of the following tryptophyllins are reported: Phe-Pro-Trp-Leu-NH2, Phe-Pro-Trp-Pro-NH2, Phe-Pro-Phe-Pro-Trp-Leu-NH2)

"Isolation, structure determination and synthesis of a novel tryptophan-containing heptapeptide (basic tryptophyllin) from the skin of Phyllomedusa rohdei " by P.C. Montecucchi, M. Vincenti, A.M. Lazzarini, L. Rusconi and V. Erspamer (1989) in: Int. J. Peptide Protein Re. 33, 391 - 395

"The structures of four tryptophyllin and three rubellidin peptides from the Australian red tree frog Litoria rubella" by . Simon T. Steinborner, Chengwei Gao, Mark J. Raftery, Russell J. Waugh, Thomas Blumenthal, John H. Bowie, John C. Wallace and Michael J. Tyler (1994), Australian J. Chemistry 47 (11), 2099

" Pachymedusa dacnicolor tryptophyllin-1 (PdT-1) structural characterization, pharmacological activity and cloning of precursor cDNA." by T.B. Chen, D.F. Orr, C. Shaw - Submitted (SEP-2002) to Swiss-Prot [(KPPAWP) Hydroxylation P3, Amidation P7] in Regulatory Peptides 117, 25-32 (2004) (available online at http://www.sciencedirect.com ). This tryptophyllin is a potent myoactive agent, relaxing mammalian arterial smooth muscle and contracting small intestinal smooth muscle at nanomolar concentrations.

" Amphibian species of the world " at  http://research.amnh.org/herpetology/amphibia/index.html . American Museum of Natural History Department of Herpetology

 

 

MISCELLANEOUS PEPTIDES

 

One additional linear peptide and three diketopiperazines were identified in methanol extracts of Phyllomedusa skin, as follows:

Origin

Peptide primary structure

Phyll. sauvagei

Leu-Met-Tyr-Tyr-Thr-Leu-Pro-Arg-Pro-Val-NH2
 

Cyclo(Tyr-Pro)
 

Cyclo(Phe-Leu)

Phyll. burmeisteri

Cyclo(Trp-Lys)

Reference:

"Phyllomedusa Skin: A Huge Factory and Store-House of a Varietry of Active Peptides" by V. Erspamer, P. Melchiorri, G. Falconieri Erspamer, P.C. Montecucchi and R. de Castiglione (1985), Peptides 6, 7-12

 

 

 

The goals of the proposed project is the following:

  • to define the biological role of tryptophyllins and some other peptides in the neuroimmunoendocrine system and in the transcriptional regulatory network.

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Seeking for: scientific collaboration (early drug research, preclinical research), co-development (clinical drug development), production, marketing