Charles G. Skinner

Activity of some 6- (substituted) purines on the development of the moss Tortella caespitosa.

Summary Of twenty-five 6-(substituted)purines tested for ability to increase the number of buds formed in the moss T. caespitosa , the following were the most active: 6-(2-furfuryl)aminopurine, 6-(2-thenyl)aminopurine, 6-benzylaminopurine, and 6- n -pentylaminopurine.

3,4-Dehydroproline, a proline antagonist

dl-3,4-Dehydroproline inhibits the growth of Lactobacillus arabinosus, Streptococcus lactis, Pediococcus cerevisiae, Leuconostoc dextranicum, and Escherichia coli, and the toxicities are competitively reversed by l-proline with inhibition indices of 3, 3, 3, 10, and 10, respectively. A noncompetitive reversal of dehydroproline toxicity by a peptide, glycylproline, is observed with E. coli, but for S. lactis, P. cerevisiae, and L. arabinosus a competitive reversal of the inhibitory effect of the analog is observed with glycylproline. Proline peptides are either more or less active than the free amino acid depending upon the assay organism. A synergistic rather than an additive effect of glycylproline in combination with proline in reversing the toxicity of dehydroproline for L. arabinosus is observed.

Stimulation of Lettuce Seed Germination by 6-(Substituted) Purines

Presoaking several varieties of seed, especially lettuce, in various 6-(substituted)aminoand thiopur ine solutions has been found to increase their rate of germination (3, 5, 6). Recently it was also reported that these purine derivatives are synergistic with gibberellin in inducing these biological responses whereas gibberellin alone was only moderately active in stimulating germination of Early Curled Simpson lettuce seed (7, 8). The mode of biochemical action of these purine derivatives and gibberellin (2) in affecting the rate of germination is as yet unknown, although it has been observed that seed activation by white light is augmented by pretreatment of the seed with various 6-(substituted)purine solutions (6). Recently Miller (4) demonstrated that maximal purine-activation of Grand Rapids lettuce seed germination is somewhat dependent on the presence of light. The action spectrum for the influence of light on germination is not necessarily the same in the presence of 6-(substituted) purines as in their absence ( 1 ) ; far-red light initiates appreciable germination after pretreatment with kinetin, even though the far-red light is less effective than red light.

2-Hydroxy derivatives of some biologically active 6-(substituted)purines

Abstract Nine new 2-hydroxy-6-(substituted)aminopurines were synthesized through a thermal condensation of 2-hydroxy-6-methylthiopurine with the appropriate amine. These derivatives did not possess the kinetin-like activities previously associated with 6-(substituted) aminopurines; however, all of these compounds inhibited the oxidase activity as well as the dehydrogenase activity of milk xanthine oxidase. In the latter system, it was also demonstrated that analogous 2-hydroxy-6-(substituted)purines may act as either competitive or noncompetitive antagonists in the presence of xanthine as the substrate.

3-Aminomethylcyclohexaneglycine, a lysine analog

Abstract A β-substituted alicyclic lysine analog, 3-aminomethylcyclohexaneglycine, was prepared from m-tolunitrile by bromination followed by alkaline hydrolysis to yield m-cyanobenzaldehyde which was then converted to 5-(m-cyanophenyl)hydantoin. Hydrogenation, followed by hydrolysis of the hydantoin, gave 3-aminomethylcyclohexaneglycine. 4-Pyridine- and 4-piperidineglycine were also synthesized by conversion of 4-pyridinecarboxaldehyde to the pyridineglycine, and subsequent hydrogenation to form the piperidineglycine. The toxic properties of the three analogs were studied in Leuconostoc dextranicnm 8086, Lactobacillus arabinosus 17-5, and Lactobacillus casei 7469. 3-Aminomethylcyclohexaneglycine, although not a highly effective antagonist, is inhibitory toward Leuc. dextranicum and L. arabinosus at a level of about 0.1 and 0.5 mg./ml., respectively, and the inhibitions are competitively reversed by lysine. Both 4-pyridineglycine and 4-piperidineglycine, even at a concentration of 1 mg./ml., were not inhibitory to any one of the three organisms studied. A previous hypothesis that lysine in forming an enzyme-substrate complex must assume a structure such that the β- and ϵ-earbons are in a trans-like conformation is consistent with the observed biological activity of 3-aminomethylcyclohexaneglycine.

Augmented inhibition by kinetin and related compounds of growth of pteridine-inhibited Lactobacillus arabinosus

Abstract Application of a previously published microbiological assay procedure for thymidine determination has been made to the detection of kinetin, certain 6-(substituted)aminopurines, and certain other related compounds, by means of the augmented inhibitory effects exerted by these compounds upon growth of pteridine-inhibited L. arabinosus in the absence of thymidine. The method can be used for bioautographic detection of such inhibitory activities on paper chromatograms.

The synthesis and biological activity of some diamino acid analogs

Abstract 3- and 4-Aminocyclohexanealanine, 4-aminocyclohexaneglycine, and the corresponding phenyl analogs have been prepared and studied as amino acid antagonists for Escherichia coli, Leuconostoc dextranicum, Lactobacillus casei, and Lactobacillus arabinosus. The compounds which were most effective include 3-aminocyclohexanealanine, m-aminophenylalanine, and p-aminophenylalanine. Growth inhibition effected by 3-aminocyclohexanealanine was reversed competitively over a range of inhibitor concentrations by increasing concentrations of lysine but not by phenylalanine, while the toxicity of the phenyl analogs was reversed over a broad range of inhibitor concentrations by phenylalanine but not by lysine. The inactivity of 4-aminocyclohexaneglycine suggests that either branching of the carbons at the β- rather than the γ-carbon sterically hinders its enzymic combination, or that the conformation of lysine on the inhibited enzyme exists in a manner such that the γ- and ϵ-carbons must be in a trans-like relationship, which is possible for the 3-aminocyclohexanealanine but not for the 4-aminocyclohexaneglycine.

Structural requirements for phenylalanine antagonism

Abstract Using the typical acetamidomalonic ester synthesis and the appropriate alkyl halides, three new amino acid analogs were prepared, 2-amino-4-ethyl-4-pentenoic acid ( II ), 2-amino-4-ethyl-4-hexenoic acid ( III ), and 2-amino-4-ethylhexanoic acid ( IV ). II was an effective antagonist of phenylalanine for Leuconostoc dextranicum , and IV is a moderately active antagonist of leucine, but III is essentially nontoxic to growth of either L. dextranicum or Escherichia coli . The stereochemical structures and conformations of these and related phenylalanine analogs were correlated with their biological activities.

3-Cyclohexene-1-dl-alanine, an analog of leucine

Abstract 3-Cyclohexene-1- dl -alanine was prepared by condensing 4-bromomethylcyclohexene and ethyl acetamidocyanoacetate, followed by hydrolysis of the resulting intermediate. The amino acid analog inhibited the growth of Leuconostoc dextranicum 8086, and its toxicity was competitively reversed by leucine (inhibition index = 100). Its inhibitory properties were correlated with the structure of the cyclohexene ring. The active form probably possesses the configuration in which carbons 1 and 6 are on opposite sides of the plane of carbons 2, 3, 4, and 5.

Synthesis of 2-fluoro-6-benzylaminopurine and other purine derivatives

Abstract The effects of a 2-fluoro substituent and of the replacement of the imidazole ring by a triazole ring upon the biological activities of a 6-(substituted)purine were determined. The 2-fluoro and 2-amino-8-aza analogs of 6-benzylaminopurine were synthesized, and the 2-fluoro but not the 2-amino-8-aza derivative was found to replace kinetin in stimulating the rate of seed germination. 2-Fluoro-6-benzylaminopurine is appreciably more toxic to microbial growth than are either 2-amino-6-benzylamino- or 6-benzylaminopurine.