The identification of a peptide in human parotid saliva particularly active in enhancing the glycolytic activity of the salivary micro-organisms

Holbrook, Ian; Molan, Peter C.

doi:10.1042/bj1490489

Cited by 39 publications

(13 citation statements)

References 26 publications

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“…5 Our previous studies on histatin 5 and several Histatins comprise a group of related neutral and of its fragments have shown that the candidacidal basic histidine-rich peptides present in human saliactivity of histatin 5 is localized at the C-terminal vary secretions and in serum. [1][2][3][4] Nearly twelve sali- [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] sequence. 23,24 The functional elements for vary histatins have been isolated from saliva, and candidacidal activity of histatin 5 have recently been their primary structures (Figure 1) determined.…”

Section: Introductionmentioning

confidence: 99%

“…[8][9][10][11] nmr of the most potent antifungal histatin sequence, They enhance the glycolytic activity of certain oral histatin 5, in aqueous and nonaqueous solutions. microorganisms, 12 and possess antimicrobial activity against a few strains of Streptococcus mutans. [13][14][15] Histatins also inhibit hemagglutination of Porphyromonas gingivalis and coaggregation between…”

Section: Introductionmentioning

confidence: 99%

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Structure of human salivary histatin 5 in aqueous and nonaqueous solutions

1998

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The solution structure of human salivary histatin 5 (D‐S‐H‐A‐K‐R‐H‐H‐G‐Y‐K‐R‐K‐F‐H‐E‐K‐H‐H‐S‐H‐R‐G‐Y) was examined in water (pH 3.8) and dimethyl sulfoxide solutions using 500 MHz homo‐ and heteronuclear two‐dimensional (2D) nmr. The resonance assignment of peptide backbone and side‐chain protons was accomplished by 2D total correlated spectroscopy and nuclear Overhauser effect (NOE) spectroscopy. The high J NH‐C αH values (≥7.4 Hz), absence of any characteristic NH‐NH(i, i + 1) or CαH‐CβH(i, i + 3) NOE connectivities, high dδ/dT values (≥0.004 ppm K−1) and the fast 1H/2H amide exchange suggest that histatin 5 molecules remain unstructured in aqueous solution at pH 3.8. In contrast, histatin 5 prefers largely α‐helical conformation in dimethyl sulfoxide solution as evident from the J NH‐C αH values (≤6.4 Hz), slow 1H/2H exchange, low dδ/dT values (≤0.003 ppm K−1) observed for amide resonances of residues 6–24, and the characteristic NH‐NH(i, i + 1) and CαH‐CβH(i, i +3) NOE connectivities. All backbone amide 15N‐1H connectivities fall within 6 ppm on the 15N scale in the 2D heteronuclear single quantum correlated spectrum, and the restrained structure calculations using DIANA suggest the prevalence of α‐helical conformations stabilized by 19 (5 → 1) intramolecular backbone amide hydrogen bonds in polar aprotic medium such as dimethyl sulfoxide. The interside‐chain hydrogen bonding and salt‐bridge type interactions that normally stabilize the helical structure of linear peptides in aqueous solutions are not observed. Histatin 5, unlike other naturally occurring antimicrobial polypeptides such as magainins, defensins, and tachyplesins, does not adopt amphiphilic structure, precluding its insertion into microbial membranes and formation of ion channels across membranes. Electrostatic (ionic type) and hydrogen bonding interactions of the positively charged and polar residues with the head groups of microbial membranes or with a membrane‐bound receptor could be the initial step involved in the mechanism of antimicrobial activity of histatins. © 1998 John Wiley & Sons, Inc. Biopoly 45: 51–67, 1998

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structure of human salivary histatin 5 in aqueous and nonaqueous solutions

1998

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“…The existence of a group of small, cationic histidinerich polypeptides (histatins) in human saliva was first observed more than two decades ago by several groups of investigators (Bonilla, 1969;Azen, 1972;Balekjian and Longton, 1973;Holbrook and Molan, 1975;Baum et al, 1976). After their discovery, they were studied at the protein level and later at the molecular genetics level (genetic polymorphism, tissue distribution at the mRNA level, and the structure of the histatin genes).…”

Section: (I) Introductionmentioning

confidence: 99%

“…Histatins have been referred to as: parotid basic (Pb) and post-parotid basic (PPb) proteins (Azen, 1973;Peters et al, 1977); histones (Balekjian and Longton, 1973); histidine-rich basic factor (Holbrook and Molan, 1975); histidine-rich acidic peptide (Hay, 1975); histidine-rich proteins (HRPs) (Baum et al, 1976;Pollock et al, 1984); and histamine-releasing peptides (Sugiyama et al, 1985). Oppenheim's group (Oppenheim et al, 1988) proposed to name these proteins "histatins", based on their primary structure and antimicrobial properties.…”

Section: (I) Introductionmentioning

confidence: 99%

Human Salivary Histatins: Promising Anti-Fungal Therapeutic Agents

Tsai

Bobek

1998

Critical Reviews in Oral Biology & Medicine

142

115

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Histatins constitute a group of small, cationic multifunctional proteins present in the saliva of human and some nonhuman primates. The most significant function of histatins may be their anti-fungal activity against Candida albicans and Cryptococcus neoformans. Histatins have been extensively studied at both the protein and gene levels. The structure-function relationship of histatins with respect to their candidacidal activity has also been studied by means of recombinant histatin variants, as well as by chemically synthesized histatin fragments. The mechanism of histatins' action on Candida albicans is not clear, but it appears to be different from that of azole-based anti-fungal drugs which interrupt ergosterol synthesis. During the past 20 years, fungal infections have become more prevalent as a result of the emergence of AIDS, as well as, paradoxically, modern medical advances. The toxicity of current anti-fungal medicine, the emergence of drug-resistant strains, and the availability of only a few types of antifungal agents are the major disadvantages of current anti-fungal therapy. Therefore, the importance of the search for new, broadspectrum anti-fungals with little or no toxicity cannot be overemphasized. The following properties make histatins promising antifungal therapeutic agents: (1) They have little or no toxicity; (2) they possess high cidal activities against azole-resistant fungal species and most of the fungal species tested; and (3) their candidacidal activity is similar to that of azole-based antifungals.Current research efforts focus on the development of improved histatins with enhanced cidal activity and stability, and of suitable and effective histatin delivery systems. These and other approaches may help to outpace the growing list of drug-resistant and opportunistic fungi causing life-threatening, disseminating diseases. The histatins with improved protective properties may also be used as components of artificial saliva for patients with salivary dysfunction.

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“…From submaxillary gland have been isolated epidermal growth factor (10), glucagon (11) or R-mesodermal growth factor (12), the protein fraction of a lipolytic factor (13) and neurite-inducing factor (14). From parotid secretions, on the other hand, a small peptide with glycolytic activity (15), Fr. AA-1 (16), fractionated from parotin (17) and a histidine Tables 1 and 2 with means±S.E.…”

Section: Discussionmentioning

confidence: 99%

Salivary peptide P-C modulates both insulin and glucagon release from isolated perfused rat pancreas.

1990

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Abstract-The effect of salivary peptide P-C, saliva-derived peptide on glucose induced insulin release was studied using perfused rat pancreas. Salivary peptide P-C (194 nM) remarkably potentiated glucose (8.3 and 16.7 mM)-induced insulin release, whereas the same concentration suppressed arginine (10 mM)-induced glucagon release. Both effects of salivary peptide P-C occurred in a concentration dependent manner. These findings suggest that salivary peptide P-C may modulate both the levels of insulin and glucagon in vivo.

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The identification of a peptide in human parotid saliva particularly active in enhancing the glycolytic activity of the salivary micro-organisms

Cited by 39 publications

References 26 publications

Structure of human salivary histatin 5 in aqueous and nonaqueous solutions

Structure of human salivary histatin 5 in aqueous and nonaqueous solutions

Human Salivary Histatins: Promising Anti-Fungal Therapeutic Agents

Salivary peptide P-C modulates both insulin and glucagon release from isolated perfused rat pancreas.

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