Lipo-amino acids

To mimic nature in its irreversible monolipidation of proteins by N-myristoylation and S-prenylation, peptides are N-acylated with fatty acids or N-alkylated with linear or branched, saturated or unsaturated aliphatic chains as well as by incorporation of newly synthesized lipo-amino acids. 

Lipo-amino acid derivatives are readily obtained in good yields by direct alkylation of amino acids esters with the related alkyl halides, e.g. farnesyl bromide, under careful control of the reaction conditions to avoid exhaustive alkylation of the amino group. 128 Alternatively, peptoid chemistry is applied for N-alkylation of glycine ester via reaction of alkyl amines, e.g. hexadecylamine, with ethyl bromoacetate. 36,98 ... 

The difficulties encountered in aminoacylation of such lipo-amino acid derivatives are similar to those of the N-alkylated amino acids (see Vol. E 22c, Sections 10.1.1 and 10.1.2), but may be even worse due to steric hindrance of the large alkyl chains. Similarly, acylation with such amino acids leads to poor yields by the use of even stronger acylating reagents, e.g. HBTU, BOP, and PyBroP, with a marked improvement by the use of the mixed anhydride method although long reaction times were required. 128 ... 

Synthesis of Lipo-Amino Acids and Enantiomeric Resolution... 

The lipo-amino acids are generally synthesized as racemic mixtures which are resolved into optically pure a-amino acids by chemical or enzymatic methods.113" 137 133 The synthesis is based on the alkylation of diethyl acetamidomalonate followed by hydrolysis and decarboxylation. 129 138 140 Also, 20% DMF has been used in the hydrolysis step, as it is suitable for industrial scale preparation. 138] Alternatively, lipidated a-amino acids are synthesized by reacting a-bromoalkanoic acid with ammonium hydroxide. 141 ... 

A3.3.2 Asymmetric Synthesis of Unsaturated Lipo-Amino Acids... 

The Na-Z- or 7V"-Boc-protected lipo-amino acids and their esters are obtained by standard protocols.113X In contrast, for the synthesis of the A -Fmoc derivatives intermediate bis-silylation and the use of Fmoc-Cl as acylating agent are recommended. 129 The standard procedure with Fmoc-OSu leads to low yields (25%) mainly due to low solubility of the amino acids. 133 Alternatively, the improved solubility of the 4-toluenesulfonate salt of the benzyl esters is exploited for reaction with Fmoc-OSu. The benzyl ester is then removed by catalytic hydrogenation, although the Fmoc group is known to be reduced under these conditions unless particular precautions are taken. 133 156-159 ... 

For a long time, amino acid or peptide containing lipids were considered as unusual components of bacteria. Isolation was mainly confined to lipo-amino acids which appeared to be transitory intermediates in cellular metabolism. Not much progress has been made on their metabolism. 

Fig. 9. Absorption spectra of several flavopro-teins compared with an action spectrum of pho-totropism (dotted line C ),39))- The spectra are arranged with respect to the position of their UV-peaks (1) succinate dehydrogenase78), (2)lipo-amide dehydrogenase179), (4) lactate oxidase111), (5) D-amino acid oxidase111), (6) flavodoxin110), (7) old yellow enzyme2), (8) ferredoxin NADP+ reductase16), (9) oxynitrilase111), (10) L-amino acid oxidase111)...

In clinical work many biological fluids have been submitted to paper electrophoretic separation. Serum and urine have been studied extensively and the results were reviewed in Volume I of this series (p. 238). Other fluids include cerebrospinal fluid (B12, B14, E6, K18), pleura] fluid (D4), gastric juice (H6), ascitic fluid (H9), synovial fluid (W3), proteins of the lens (F4, W9, W10), aqueous humor of the eye (W12, W24), edema liquid (W23), and pericardiac effusion (G2). Apart from the general separation of plasma proteins, work has been done on special protein groups, such as lipo- and glycoproteins, muco-proteins, hemoglobins (H19), coagulation factors (05), and on other components, such as amino acids. 

The function of a surfactant depends on its hydrophilicity-lipo-philicity balance (HLB). Efficient emulsification of oil generally requires a low HLB, while the whipping characteristic arises at a larger HLB. This chapter is an attempt to prepare proteinaceous surfactants with different HLBs by the enzymatic attachment of amino acid esters with different lipophilicity. For this purpose L-leucine n-alkyl esters (Leu-OQ), the alkyl chain length, i, varying from 2 to 12, were used. As... 

In both cases, amino acids that can modulate chemical-physical properties such as lipo-philicity (like 11, present in saquinavir and nelfmavir), can produce supplementary bonds (like 12 and 13 [42]), or can induce stereochemical constraint (like 14 [43]) are frequently used (Fig. 15). The design and synthesis of conformationally constrained amino acids as scaffolds for peptidomimetics synthesis, has been recently reviewed by Hanessian [44]. 

Three precursor proteins of O. p. have been identified and sequenced. The first, preproopiomelanocortin, is the source of corticotropin (ACTH) and -lipo-tropin (see Hormones). These hormones are cleaved to smaller peptides 3-endorphin is released from P-li-potropin. The second and third precursors are preproenkephalins A and B (PPE A and PPE B). PPE A contains four copies of Met-enkephalin, one of Leu-enkephalin, and two extended Met-enkephalins with six and seven amino acids, respectively. It is also the source of adrenorphin, and other active peptides. PPE B is the precursor of a-neo-endorphin, dynorphin, and PH-8P (a predominant O.p. in brain). 

Attempts were made to isolate the TBG. A preliminary purification from serum by ion-exchange chromatographic analysis on a Dowex-I column equilibrated with acetate buffer (pH 4.5) was followed by repeated ammonium sulfate precipitation, chromatographic analysis on dimethylaminoethyl-cellulose resin, and electrophoresis on cellulose columns. These attempts finally yielded a preparation homogeneous on electrophoresis and in the ultracentrifuge. The amino acid composition and the secondary structure of TBG is not known, and it is still debated whether it is a lipo-or glycoprotein. 

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