Multivariate design and evaluation of a set of RGRPQ-derived innate immunity peptides.
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.
Drobni
Mirva
M
Department of Odontology/Cariology, UmeA University, SE-901 87 UmeA, Sweden.
Olsson
Ing-Marie
IM
Eriksson
Christer
C
Almqvist
Fredrik
F
Strömberg
Nicklas
N
D000190:Actinomyces / Q000276:immunology / Q000472:pathogenicity; D000595:Amino Acid Sequence; D000641:Ammonia / Q000378:metabolism; D001422:Bacterial Adhesion / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D009842:Oligopeptides / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D055232:Proline-Rich Protein Domains; D021281:Quantitative Structure-Activity Relationship; D012463:Saliva / Q000276:immunology; D012471:Salivary Proteins and Peptides / Q000737:chemistry / Q000276:immunology; D013291:Streptococcus / Q000276:immunology / Q000472:pathogenicity
D009842:Oligopeptides; D019151:Peptide Library; D010455:Peptides; D012471:Salivary Proteins and Peptides; D000641:Ammonia