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Synthesis, conformation and biological activity of centrally modified pseudopeptidic analogues of For-Met-Leu-Phe-OMe

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Summary.

For-Met-βAlaψ[CSNH]-Phe-OMe (3), For-Met-βAlaψ[CH2NH]-Phe-OMe (5), For-Met-NH-pC6H4-SO2-Phe-OMe (8a), For-Met-NH-mC6H4-SO2-Phe-OMe (8b) and the corresponding N-Boc precursors (2, 4, 7a, b) have been synthesized and their activity towards human neutrophils has been evaluated in comparison with that shown by the reference tripeptide For-Met-Leu-Phe-OMe (fMLF-OMe). Chemotaxis, lysozyme release and superoxide anion production have been measured. 1H NMR titration experiments and IR spectra have been discussed in order to ascertain the preferred solution conformation adopted by the tripeptide 3 with particular reference to the presence of a folded conformation centred at the centrally positioned thionated β-residue.

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References

  • M Aschi G Lucente F Mazza A Mollica E Morera M Nalli M Paglialunga Paradisi (2003) ArticleTitlePeptide backbone folding induced by Cα-tetrasubstituted cyclic α-aminoacids 4-amino-1,2-dithiolane-4-carboxylic acid (Adt) and 1-aminocyclopentane-1-carboxylic acid (Ac5c). A joint computational and experimental study Org Biomol Chem 1 1980–1988 Occurrence Handle12945783 Occurrence Handle10.1039/b212247b Occurrence Handle1:CAS:528:DC%2BD3sXkvFWqtL0%3D

    Article  PubMed  CAS  Google Scholar 

  • M Aschi A Mollica G Lucente M Paglialunga Paradisi F Mazza (2006) ArticleTitleConformational properties of β-residue-containing oligopeptides in apolar solvent J Mol Struct 785 176–181 Occurrence Handle10.1016/j.molstruc.2005.10.009 Occurrence Handle1:CAS:528:DC%2BD28XitVKntro%3D

    Article  CAS  Google Scholar 

  • A Calcagni E Gavuzzo G Lucente F Mazza E Morera M Paglialunga Paradisi D Rossi (2000) ArticleTitlePeptides containing the sulfonamide junction. 2. Structure and conformation of Z-Tau-Pro-D-Phe-NhiPr Biopolymers 54 379–387 Occurrence Handle10951324 Occurrence Handle10.1002/1097-0282(200011)54:6<379::AID-BIP20>3.0.CO;2-N Occurrence Handle1:CAS:528:DC%2BD3cXnvVGnt7k%3D

    Article  PubMed  CAS  Google Scholar 

  • MP Cava MI Levinson (1985) ArticleTitleThionation reactions of Lawesson’s reagent Tetrahedron 41 5061–5087 Occurrence Handle10.1016/S0040-4020(01)96753-5 Occurrence Handle1:CAS:528:DyaL28XhsVOrurw%3D

    Article  CAS  Google Scholar 

  • AR Dentino PA Raj KK Bhandary ME Wilson MJ Levine (1991) ArticleTitleRole of peptide backbone conformation on biological activity of chemotactic peptides J Biol Chem 266 18460–18468 Occurrence Handle1917969 Occurrence Handle1:CAS:528:DyaK3MXlsFKru7o%3D

    PubMed  CAS  Google Scholar 

  • C Gennari M Gude D Potenza U Piarulli (1998) ArticleTitleHydrogen bonding donor/acceptor scales in β-sulfonamidopeptides Chem Eur J 4 1924–1931 Occurrence Handle10.1002/(SICI)1521-3765(19981002)4:10<1924::AID-CHEM1924>3.0.CO;2-P Occurrence Handle1:CAS:528:DyaK1cXmvVOmtrc%3D

    Article  CAS  Google Scholar 

  • C Giordano G Lucente M Nalli G Pagani Zecchini M Paglialunga Paradisi K Varani S Spisani (2003) ArticleTitleSynthesis and activity of HCO-Met-Leu-Phe-OMe analogues containing β-alanine or taurine at the central position Farmaco 58 1121–1130 Occurrence Handle14572863 Occurrence Handle10.1016/S0014-827X(03)00165-4 Occurrence Handle1:CAS:528:DC%2BD3sXot12isbg%3D

    Article  PubMed  CAS  Google Scholar 

  • C Giordano G Lucente A Mollica M Nalli G Pagani Zecchini M Paglialunga Paradisi E Gavuzzo F Mazza S Spisani (2004) ArticleTitleHybrid α/β3-peptides with proteinogenic side chains. Monosubstituted analogues of the chemotactic tripeptide For-Met-Leu-Phe-Ome J Peptide Sci 10 510–523 Occurrence Handle10.1002/psc.562 Occurrence Handle1:CAS:528:DC%2BD2cXmvVagtbw%3D

    Article  CAS  Google Scholar 

  • DJ Hill JM Mio RB Prince TS Hughes JS Moore (2001) ArticleTitleA field guide to foldamers Chem Rev 101 3893–4011 Occurrence Handle11740924 Occurrence Handle10.1021/cr990120t Occurrence Handle1:CAS:528:DC%2BD3MXovFagtrk%3D

    Article  PubMed  CAS  Google Scholar 

  • M Hòllosi M Zewdu E Kollàt Z Majer M Kajtàr G Batta K Koevèr P Sàndor (1990) ArticleTitleIntramolecular H-bonds and thioamide rotational isomerism in thiopeptides Int J Peptide Res 36 173–181 Occurrence Handle10.1111/j.1399-3011.1990.tb00963.x

    Article  Google Scholar 

  • D Krumme H Tschesche (1999) ArticleTitleSynthesis and reduction of endothiodipeptides containing malonic acid derivatives Tetrahedron 55 3007–3018 Occurrence Handle10.1016/S0040-4020(99)00084-8 Occurrence Handle1:CAS:528:DyaK1MXhslKmu7k%3D

    Article  CAS  Google Scholar 

  • G Lajoie JL Kraus (1984) ArticleTitleRapid and efficient method for the N-formylation of C-blocked peptides Peptides 5 653–654 Occurrence Handle6473175 Occurrence Handle10.1016/0196-9781(84)90099-8 Occurrence Handle1:CAS:528:DyaL2cXlslWksLg%3D

    Article  PubMed  CAS  Google Scholar 

  • Y Le Y Yang Y Cui H Yazawa W Gong C Qiu JM Wang (2002) ArticleTitleReceptors for chemotactic formyl peptides as pharmacological targets Int Immunopharmacol 2 1–13 Occurrence Handle11789660 Occurrence Handle10.1016/S1567-5769(01)00150-3 Occurrence Handle1:CAS:528:DC%2BD38Xjt1ylsw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • H-J Lee Y-S Choi K-B Lee J Park C-J Yoon (2003) ArticleTitleHydrogen bonding abilities of thioamide J Phys Chem A 106 7010–7017 Occurrence Handle10.1021/jp025516e Occurrence Handle1:CAS:528:DC%2BD38XkvF2qtbg%3D

    Article  CAS  Google Scholar 

  • Lowik DWPM, Liskamp RMJ (2000) Synthesis of α- and β-substituted aminoethane sulphonamide arginine-glycine mimics. Eur J Org Chem: 1219–1228

  • HL Malech JI Gallin (1987) ArticleTitleNeutrophils in human diseases N Engl J Med 317 687–694 Occurrence Handle3041216 Occurrence Handle1:STN:280:DyaL2szhsFaisQ%3D%3D Occurrence Handle10.1056/NEJM198709103171107

    Article  PubMed  CAS  Google Scholar 

  • BK Min H-J Lee YS Choi J Park C-J Yoon J-A Yu (1998) ArticleTitleA comparative study on the hydrogen bonding ability of amide and thioamide using near IR spectroscopy J Mol Struct 471 283–288 Occurrence Handle10.1016/S0022-2860(98)00488-8 Occurrence Handle1:CAS:528:DyaK1cXnvV2gtLY%3D

    Article  CAS  Google Scholar 

  • A Mollica M Paglialunga Paradisi D Torino S Spisani G Lucente (2006) ArticleTitleHybrid α/β-peptides: For-Met-Leu-Phe-OMe analogues containing geminally disubstituted β2,2- and β3,3-aminoacids at the central position Amino Acids 30 453–459 Occurrence Handle16547648 Occurrence Handle10.1007/s00726-006-0260-y Occurrence Handle1:CAS:528:DC%2BD28Xls1ehu70%3D

    Article  PubMed  CAS  Google Scholar 

  • G Pagani Zecchini E Morera M Nalli M Paglialunga Paradisi G Lucente S Spisani (2001) ArticleTitleSynthesis and activity on human neutrophil functions of fMLF-OMe analogs containing alkyl spacers at the central position Farmaco 56 851–858 Occurrence Handle11765037 Occurrence Handle10.1016/S0014-827X(01)01140-5 Occurrence Handle1:CAS:528:DC%2BD3MXosFOju7k%3D

    Article  PubMed  CAS  Google Scholar 

  • ER Prossnitz RD Ye (1997) ArticleTitleThe N-formyl peptide receptor: a model for the study of chemoattractant receptor structure and function Pharmacol Ther 74 73–102 Occurrence Handle9336017 Occurrence Handle10.1016/S0163-7258(96)00203-3 Occurrence Handle1:CAS:528:DyaK2sXkvFChsL4%3D

    Article  PubMed  CAS  Google Scholar 

  • RS Rathore (2005) ArticleTitleConformational investigations on analogs of inflammation response inducing chemotactic tripeptide fMLP Biopolymers (Pept Sci) 80 651–664 Occurrence Handle10.1002/bip.20231 Occurrence Handle1:CAS:528:DC%2BD2MXhtFSrsbbP

    Article  CAS  Google Scholar 

  • RA Shaw E Kollàt M Hòllosi HH Mantsch (1995) ArticleTitleHydrogen bonding and isomerization in thioamide peptide derivatives Spectrochim Acta Part A 51 1399–1412 Occurrence Handle10.1016/0584-8539(95)01448-9

    Article  Google Scholar 

  • DB Sherman AF Spatola (1990) ArticleTitleCompatibility of thioamides with reverse turn features: synthesis and conformational analysis of two model cyclic pseudopeptides containing thioamides as backbone modifications J Am Chem Soc 112 433–441 Occurrence Handle10.1021/ja00157a064 Occurrence Handle1:CAS:528:DyaK3cXjs1CntA%3D%3D

    Article  CAS  Google Scholar 

  • HJ Showell RJ Freer SH Zigmond E Schiffmann S Aswanikumar B Corcoran EL Becker (1976) ArticleTitleThe structure-activity relations of synthetic peptides as chemotactic factors and inducers of lysosomal enzyme secretion for neutrophils J Exp Med 143 1154–1169 Occurrence Handle1262785 Occurrence Handle10.1084/jem.143.5.1154 Occurrence Handle1:CAS:528:DyaE28XktlWntbs%3D

    Article  PubMed  CAS  Google Scholar 

  • T Sifferlen M Rueping K Gademann B Jaun D Seebach (1999) ArticleTitleβ-Thiopeptides: synthesis, NMR solution structure, CD spectra, and photochemistry Helv Chim Acta 82 2067–2091 Occurrence Handle10.1002/(SICI)1522-2675(19991215)82:12<2067::AID-HLCA2067>3.0.CO;2-5 Occurrence Handle1:CAS:528:DC%2BD3cXktFOntg%3D%3D

    Article  CAS  Google Scholar 

  • TT Tran J Zeng H Treutlein AW Burgess (2002) ArticleTitleEffects of thioamide substitutions on the conformation and stability of a- and 310-helices J Am Chem Soc 124 5222–5230 Occurrence Handle11982387 Occurrence Handle10.1021/ja011916o Occurrence Handle1:CAS:528:DC%2BD38Xislahu74%3D

    Article  PubMed  CAS  Google Scholar 

  • SH Zigmond JG Hirsc (1973) ArticleTitleLeukocyte locomotion and chemotaxis. New methods for evaluation and demonstration of cell-derived chemotactic factor J Exp Med 137 387–410 Occurrence Handle4568301 Occurrence Handle10.1084/jem.137.2.387 Occurrence Handle1:CAS:528:DyaE3sXpsFyrtQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

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

    G. Lucente, A. Masi, M. Paglialunga Paradisi & A. Sansone

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

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

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

    S. Spisani

Authors
  1. C. Giordano
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  2. G. Lucente
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  3. A. Masi
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  4. M. Paglialunga Paradisi
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  5. A. Sansone
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  6. S. Spisani
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Giordano, C., Lucente, G., Masi, A. et al. Synthesis, conformation and biological activity of centrally modified pseudopeptidic analogues of For-Met-Leu-Phe-OMe. Amino Acids 33, 477–487 (2007). https://doi.org/10.1007/s00726-006-0422-y

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  • DOI: https://doi.org/10.1007/s00726-006-0422-y

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