Drobni Mirva, Olsson Ing-Marie, Eriksson Christer, Almqvist Fredrik, Strömberg Nicklas
Department of Odontology/Cariology, UmeA University, SE-901 87 UmeA, Sweden.
J Biol Chem. 2006 Jun 2;281(22):15164-71. doi: 10.1074/jbc.M511727200. Epub 2006 Apr 4.
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.
口腔共生菌戈登氏链球菌可将唾液中的PRP - 1多肽进行蛋白水解，生成RGRPQ天然肽。RGRPQ的精氨酸（Arg）和谷氨酰胺（Gln）末端分别对戈登氏链球菌SK12介导的氨生成和增殖以及内氏放线菌T14V介导的黏附抑制和解吸至关重要。在此，我们应用了（i）一种多变量方法，使用在第2、3和4位氨基酸同时变化的与RGRPQ相关的肽，以及（ii）对RGRPQ进行大小、N端和C端修饰，以生成结构活性信息。虽然N端精氨酸基序介导氨生成，与肽的大小无关，但其他反应或多或少需要全长肽基序。黏附抑制和解吸的基序相同。黏附和增殖基序同样需要第4位氨基酸具有疏水性/低极性，但分别对第2/3位氨基酸的亲水性或疏水性特征有不同要求；分别具有小/亲水性和第2和3位亲水性氨基酸的极性肽具有高黏附抑制/解吸活性，而具有大/疏水性第2和3位氨基酸的亲脂性肽具有高增殖活性。因此，虽然RIWWQ具有增强的增殖能力，但消除了黏附/解吸活性，预计用亲水性第2和3位氨基酸设计的肽会表现出相反的行为。此外，一种模拟所有三种反应的RGRPQ应分别模拟小的亲水性、大的含氮性以及疏水性/低极性的第2、3和4位氨基酸。符合这些标准的肽在所有三种反应中提高了1 - 1.6倍。因此，可能生成模拟物以及具有不同增殖和黏附活性的肽，用于在生物膜模型中进行评估。
