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Chemotactic tripeptides incorporating at position 2 α-aminoacid residues with unsaturated side chains

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Summary.

New N-For-Met-Leu-Phe-OMe (fMLF-OMe) analogues incorporating three different γ-δ-didehydro-α-aminoacid residues (namely: Alg = (S)-Allylglycine; Dag = Diallylglycine; Cpg = 1-Aminocyclopent-3-ene-1-carboxylic acid) replacing the native (S)-Leucine have been synthesized and their activity towards human neutrophils has been evaluated in comparison with that shown by the reference tripeptide fMLF-OMe. Chemotaxis, lysozyme release and superoxide anion production have been measured. 1H NMR titration experiments and NOESY spectrum of the Cpg containing model 10 have been discussed in order to ascertain the preferred solution conformations. A fully extended (C5) conformation at position 2 and a folded conformation with two consecutive γ-turns (C7 structure) have been proposed for the Dag and Cpg containing tripeptides, respectively.

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Abbreviations

Boc:

tert-butyloxycarbonyl

BOP:

(benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate

DMF:

dimethylformamide

EDC:

1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride

EEDQ:

ethyl 2-ethoxy-1,2-dihydro-1-quinolinecarboxylate

HOBT:

1-hydroxybenzotriazole

KRPG:

Krebs-Ringer phosphate containing 0.1% w/v d-glucose

RCM:

ring-closing metathesis

TEA:

triethylamine

TFA:

trifluoroacetic acid

TLC:

thin-layer chromatography

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Authors and Affiliations

  1. Dipartimento di Studi Farmaceutici, Università degli Studi di Roma ‘La Sapienza’, Rome, Italy

    G. Lucente, M. P. Paradisi, A. Sansone & D. Torino

  2. Istituto di Chimica Biomolecolare del CNR, c/o Dipartimento di Studi Farmaceutici, Università degli Studi di Roma ‘La Sapienza’, Rome, Italy

    G. Lucente, M. P. Paradisi & C. Giordano

  3. Dipartimento di Biochimica e Biologia Molecolare, Università di Ferrara, Ferrara, Italy

    S. Spisani

Authors
  1. G. Lucente
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  2. M. P. Paradisi
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  3. C. Giordano
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  4. A. Sansone
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  5. D. Torino
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  6. S. Spisani
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Authors’ address: Prof. Gino Lucente, Università degli Studi di Roma ‘La Sapienza’, P.le A. Moro 5, 00185 Rome, Italy

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Lucente, G., Paradisi, M., Giordano, C. et al. Chemotactic tripeptides incorporating at position 2 α-aminoacid residues with unsaturated side chains. Amino Acids 35, 329–338 (2008). https://doi.org/10.1007/s00726-007-0621-1

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  • DOI: https://doi.org/10.1007/s00726-007-0621-1

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