Disease relevance of Phe-Phe

• This structural change allows better access of the Phe-Phe linkages to cathepsin D. This scheme represents an effective way of generating the immunodominant peptide which sensitizes T-cells for the autoimmune response in demyelinating disease [1].
• A series of glycopeptidemimetics based on the hydroxyethylene Phe-Phe isostere have been synthesized and evaluated for their ability to inhibit the enzyme HIV-1 protease [2].

High impact information on Phe-Phe

• Specificity was further shown by the finding that no significant interaction was observed in yeast expressing LexA-Abeta bait when the B42 transactivation domain was fused to an Abeta fragment with Phe-Phe at residues 19 and 20 replaced by Thr-Thr (AbetaTT), a finding that is consistent with in vitro observations made by others [3].
• RMCP I was more prone than chymotrypsin to hydrolyze peptide bonds consisting of Leu-Xaa or two hydrophobic residues--e.g., Phe-Phe [4].
• Patients with the Ile/Ile genotype had an increased risk for invasive disease (stage II-IV; OR = 2.13, 95% CI = 1.04-4.39) or metastatic disease (stage III and IV; OR = 2.31, 95% CI = 1.06-5.05) compared with those with the Phe/Phe genotype [5].
• The importance of two Phe-Phe pairs in MBP to its interactions with lipids was investigated by separately mutating each pair to Ala-Ala [6].
• We also show that mutation of residues Ser(338) to Ala or Tyr(340)-Tyr(341) to Phe-Phe immediately amino-terminal to the catalytic domain abrogates activation of both the wild type and zinc finger mutant Raf by both EGF/4beta-12-O-tetradecanoylphorbol-13-acetate and nocodazole [7].

Biological context of Phe-Phe

• A study of the time course of the hydrolysis showed that the reaction was biphasic; nearly all of the protein was cleaved at Phe-Phe (88-89) before significant cleavages at other sites occurred [8].
• Cerebral aspartic peptidases show identical substrate specificity, cleaving the Leu10-Leu bond in RSTP and Phe-Phe in SP and peptide I-III, and not splitting angiotensins I and II [9].

Anatomical context of Phe-Phe

• Studies with guinea pig and rabbit myelin basic protein fragments showed that a region encompassing the central Phe-Phe (87-88) sequence is obligatory, but not sufficient, for reactivity with antibody 18.25 [10].
• An intramolecularly quenched fluorogenic peptide containing o-aminobenzoyl (Abz) and ethylenediamine 2,4-dinitrophenyl (Eddnp) groups at amino- and carboxyl-terminal amino acid residues, Abz-Lys-Pro-Ile-Glu-Phe-Phe-Arg-Leu-Eddnp, was hydrolyzed by purified human pepsin, gastricsin, and gastric juice uniquely at the Phe-Phe bond [11].
• These results provide evidence that in intestinal epithelium, hydrolysis of Phe-Phe and maltose does not occur on the cell surface with release of the hydrolyzed products to the medium [12].
• We examined whether in-vivo expression of the variant compared to the wild-type Phe/Phe genotype at codon 124 of the 5-HT1B receptor in human temporal arteries modifies their agonist-induced contraction [13].

Associations of Phe-Phe with other chemical compounds

• Design, structure-activity, and molecular modeling studies of potent renin inhibitory peptides having N-terminal Nin-For-Trp (Ftr): angiotensinogen congeners modified by P1-P1' Phe-Phe, Sta, Leu psi[CH(OH)CH2]Val or leu psi[CH2NH]Val substitutions [14].
• Brain cathepsin D, purified by affinity chromatography on Sepharose pepstatin columns, was incubated with synthetic peptides corresponding to the susceptible regions of the myelin basic protein encompassing the two Phe-Phe bonds [15].
• Kallistatin is a unique serine proteinase inhibitor (serpin) with Phe-Phe residues at the P2 and P1 positions [16].
• N-Terminal sodium phosphonate derivatives Na3O3PCH2CONHR (R-Leu, Phe, or Tyr) and Na3O3PCH2CONHR-R (R-R = Leu-Phe, Phe-Leu, Phe-Phe, and Phe-Tyr) were synthesized [17].

Gene context of Phe-Phe

• Specificity of human tissue kallikrein towards substrates containing Phe-Phe pair of amino acids [18].
• Specifically, Ac-Ftr-Pro-Phe-His-Phe-Phe-Val-Ftr-NH2 (1) provided a potent (KI = 2.7 X 10(-8) M) P1-P1' Phe-Phe substituted renin inhibitor to initiate these studies [14].
• Rapid cleavage of bovine and guinea pig myelin basic proteins by pepsin at pH 6.0 is limited to the Phe-Phe bond in the middle of the molecule [19].
• It was found that the Aurora A Ile/Ile genotype was significantly associated with increased risk of breast carcinoma occurrence [odds ratio (OR) 1.66; 95% confidence interval (95% CI) 1.29-2.12] compared with the Phe/Phe or Phe/Ile genotype [20].
• The results show that both of the decapapetides were cleaved by cathepsin D at the Phe-Phe linkages [15].

Analytical, diagnostic and therapeutic context of Phe-Phe

• The isolated cDNA was subjected to site-directed mutagenesis to replace a Val-Ile dipeptide with Phe-Phe to increase the chymosin sensitivity of the protein [21].

References