Multivariate design and evaluation of a set of RGRPQ-derived innate immunity peptides
2006 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, Vol. 281, no 22, 15164-15171 p.Article in journal (Refereed) Published
Oral commensal Streptococcus gordonii proteolytically cleave the salivary PRP-1 polypeptide into an RGRPQ innate peptide. The Arg and Gln termini are crucial for RGRPQ-mediated ammonia production and proliferation by S. gordonii SK12 and adhesion inhibition and desorption by Actinomyces naeslundii T14V, respectively. Here we have applied (i) a multivariate approach using RGRPQ-related peptides varied at amino acids 2, 3, and 4 simultaneously and (ii) size and N- and C-terminal modifications of RGRPQ to generate structure activity information. While the N-terminal arginine motif mediated ammonia production independent of peptide size, other responses required more or less full-length peptide motifs. The motifs for adhesion inhibition and desorption were the same. The adhesion and proliferation motifs required similarly a hydrophobic/low polarity amino acid 4 but differentially a hydrophilic or hydrophobic character of amino acids 2/3, respectively; polar peptides with small/hydrophilic and hydrophilic amino acids 2 and 3, respectively, had high adhesion inhibition/desorption activity, and lipophilic peptides with large/hydrophobic amino acids 2 and 3 had high proliferation activity. Accordingly, while RIWWQ had increased proliferation but abolished adhesion/desorption activity, peptides designed with hydrophilic amino acids 2 and 3 were predicted to behave in the opposite way. Moreover, a RGRPQ mimetic for all three responses should mimic small hydrophilic, large nitrogen-containing, and hydrophobic/low polarity amino acids 2, 3, and 4, respectively. Peptides fulfilling these criteria were 1-1.6-fold improved in all three responses. Thus, both mimetics and peptides with differential proliferation and adhesion activities may be generated for evaluation in biofilm models.
Place, publisher, year, edition, pages
2006. Vol. 281, no 22, 15164-15171 p.
Actinomyces/immunology/pathogenicity, Amino Acid Sequence, Ammonia/metabolism, Bacterial Adhesion/drug effects, Drug Design, Humans, Immunity; Natural, Oligopeptides/chemistry/*immunology/pharmacology, Peptide Library, Peptides/chemistry/immunology, Quantitative Structure-Activity Relationship, Saliva/immunology, Salivary Proteins/chemistry/immunology, Streptococcus/immunology/pathogenicity
IdentifiersURN: urn:nbn:se:umu:diva-10654DOI: doi:10.1074/jbc.M511727200PubMedID: 16595685OAI: oai:DiVA.org:umu-10654DiVA: diva2:150325
Kemi, kemometri, odontologi, kariologi2007-04-192007-04-192009-10-01Bibliographically approved