- Binding Methylarginines and Methyllysines as Free Amino Acids: A Comparative Study of Multiple Host Classes**
-
Methylated free amino acids are an important class of targets for host-guest chemistry that have recognition properties distinct from those of methylated peptides and proteins. We present comparative binding studies for three different host classes that are each studied with multiple methylated arginines and lysines to determine fundamental structure-function relationships. The hosts studied are all anionic and include three calixarenes, two acyclic cucurbiturils, and two other cleft-like hosts, a clip and a tweezer. We determined the binding association constants for a panel of methylated amino acids using indicator displacement assays. The acyclic cucurbiturils display stronger binding to the methylated amino acids, and some unique patterns of selectivity. The two other cleft-like hosts follow two different trends, shallow host (clip) following similar trends to the calixarenes, and the other more closed host (tweezer) binding certain less-methylated amino acids stronger than their methylated counterparts. Molecular modelling sheds some light on the different preferences of the various hosts. The results identify hosts with new selectivities and with affinities in a range that could be useful for biomedical applications. The overall selectivity patterns are explained by a common framework that considers the geometry, depth of binding pockets, and functional group participation across all host classes.
- Warmerdam, Zoey,Kamba, Bianca E.,Le, My-Hue,Schrader, Thomas,Isaacs, Lyle,Bayer, Peter,Hof, Fraser
-
-
- Peptide Tyrosinase Activators
-
Peptides that increase melanin synthesis are provided. These peptides include pentapeptides YSSWY, YRSRK, and their variants. The peptides may activate the enzymatic activity of tyrosinase to increase melanin synthesis. The pharmaceutical, cosmetic, and other compositions including the peptides are also provided. The methods of increasing melanin production in epidermis of a subject are provided where the methods include administering compositions comprising an amount of one or more peptides effective to increase the melanin production. The methods also include treating vitiligo or other hypopigmentation disorders with compositions including one or more peptides.
- -
-
-
- Design and synthesis of novel sulfonamide-containing bradykinin hB 2 receptor antagonists. 2. Synthesis and structure-activity relationships of α,α-cycloalkylglycine sulfonamides
-
Recently we reported on the design and synthesis of a novel class of selective nonpeptide bradykinin (BK) B2 receptor antagonists (J. Med. Chem. 2006, 3602-3613). This work led to the discovery of MEN 15442, an antagonist with subnanomolar affinity for the human B2 receptor (hB2R), which also displayed significant and prolonged activity in vivo (for up to 210 min) against BK-induced bronchoconstriction in the guinea-pig at a dose of 300 nmol/kg (it), while demonstrating only a slight effect on BK-induced hypotension. Here we describe the further optimization of this series of compounds aimed at maximizing the effect on bronchoconstriction and minimizing the effect on hypotension, with a view to developing topically delivered drugs for airway diseases. The work led to the discovery of MEN 16132, a compound which, after intratracheal or aerosol administration, inhibited, in a dose-dependent manner, BK-induced bronchoconstricton in the airways, while showing minimal systemic activity. This compound was selected as a preclinical candidate for the topical treatment of airway diseases involving kinin B2 receptor stimulation.
- Fattori, Daniela,Rossi, Cristina,Fincham, Christopher I.,Caciagli, Valerio,Catrambone, Fernando,D'Andrea, Piero,Felicetti, Patrizia,Gensini, Martina,Marastoni, Elena,Nannicini, Rossano,Paris, Marielle,Terracciano, Rosa,Bressan, Alessandro,Giuliani, Sandro,Maggi, Carlo A.,Meini, Stefania,Valenti, Claudio,Quartara, Laura
-
p. 550 - 565
(2007/10/03)
-
- Spontaneous N epsilon-methylation of L-lysine by formaldehyde.
-
It has been found that the conversion of L-lysine (1) into its corresponding N epsilon-methylated derivatives, mainly N epsilon-mono-methyl-L-lysine (5; MML), but also N epsilon, N epsilon-dimethyl-L-lysine (DML) and N epsilon, N epsilon, N epsilon-trimethyl-L-lisine (TML) takes place by treatment with formaldehyde in spontaneous reaction. The identification of N epsilon-methylated lysines was carried out by different chromatographic and spectroscopic methods. This spontaneous N epsilon-methylation of L-lysine by formaldehyde may also play an important role in living organisms.
- Tyihak,Trezl,Rusznak
-
-