An antibiotic R106 represented by the general formula I): ##STR1## wherein: R is methyl or ethyl; X.sub.1 is MePhe, .beta.-HOMePhe or Phe; X.sub.2 is allo-Ile, Val or Leu; X.sub.3 is MeVal or Val; X.sub.4 is .beta.-HOMeVal, .gamma.-HOMeVal, MeVal, Val, N,.beta.-MeAsp, .beta.-HOMePhe, MePhe, MeDH.sub.2,3 Val or MeDH.sub.3,4 Val is produced by a process which comprises culturing a strain of the genus Aureobasidium that is capable of producing the said antibiotic R106 and collecting the said antibiotic from the fermentation broth. The antibiotic R106 compounds are useful in the treatment of fungal infection.
This application is a division of application Ser. No. 07/657,811 filed Feb. 2, 1991, (now U.S. Pat. No. 5,158,876) which is a division of application Ser. No. 379,629, filed Jul. 13, 1989, now U.S. Pat. No. 5,057,493.
Priority Data
Jul 19, 1988 [JP] 63-180095 Feb 16, 1989 [JP] 1-36736 Jun 19, 1989 [JP] 1-158112
The invention provides an isolated gene coding for a protein regulating aureobasidin sensitivity; a process for cloning the gene with the use of the gene or a part of the same as a probe; a nucleic acid probe being hybridizable with the gene; an antisense DNA or RNA of the gene; a recombinant or transformant having the gene contained therein; an isolated protein regulating aureobasidin sensitivity and a process for producing the same by using the transformant; an antibody for the protein; a process for detecting the protein or the gene; and a process for screening an antimycotic by using the protein or the transformant. The invention is useful in the diagnosis and treatment of diseases including mycoses.
A gene associated with sensitivity to the antimycotic agent, aureobasidin A, has been isolated. The gene can be detected in a variety of cell types, and variant forms of the gene have been identified in mutant yeast strains. The proteins encoded by these genes are useful in diagnosing and treating mycoses.
A process for removing .beta.-hydroxy groups from .beta.-hydroxy-containing compounds is disclosed. The process involves the use of a retro-aldol-promoting reagent selected from the group of trimethylamine-N-oxide, triethylamine-N-oxide, trimethylamine-N-oxide-hydrate, and trimethylamine-hydrate and requires dissolution of the substrate in an aprotic solvent and reaction under elevated temperatures. The process is broadly applicable to a variety of substrates including complex cyclic peptides, linear peptides, and non-peptides.
Provided are pharmaceutical formulations, and methods of inhibiting fungal and parasitic activity using a compound of formula I: ##STR1## wherein: R.sup.z1 is hydrogen, --CH.sub.2 OH, --CHOHCH.sub.3 or --CHOHCH.sub.2 C(O)NH.sub.2 ; R.sup.z2 is hydrogen, --CH.sub.2 OH or --CHOHCH.sub.3 ; R.sup.z3 is hydrogen or methyl; R.sup.x1 is hydrogen, hydroxy or O--R.sup.x1' ; R.sup.x1' is C.sub.1 -C.sub.6 alkyl, benzyl, --(CH.sub.2).sub.2 Si(CH.sub.3).sub.3, --CH.sub.2 CH.dbd.CH.sub.2, --CH.sub.2 CHOHCH.sub.2 OH, --(CH.sub.2).sub.a COOH, --(CH.sub.2).sub.b NR.sup.w1 R.sup.w2, --(CH.sub.2).sub.c POR.sup.w3 R.sup.w4 or --[(CH.sub.2).sub.2 O].sub.d --(C.sub.1 -C.sub.6)alkyl; a, b and c are independently 1, 2, 3, 4, 5 or 6; R.sup.w1 and R.sup.w2 are independently hydrogen, C.sub.1 -C.sub.6 alkyl, or R.sup.w1 and R.sup.w2 combine to form --CH.sub.2 (CH.sub.2).sub.e CH.sub.2 --; R.sup.w3 and R.sup.w4 are independently hydroxy, or C.sub.1 -C.sub.6 alkoxy; d is 1 or 2; e is 1, 2 or 3; R.sup.x2, R.sup.y1, R.sup.y2, R.sup.y3 and R.sup.y4 are independently hydroxy or hydrogen; R.sup.0 is hydroxy, --OP(O)(OH).sub.2 or a group of the formulae: ##STR2## R.sup.1 is C.sub.1 -C.sub.6 alkyl, phenyl, p-halo-phenyl, p-nitrophenyl, benzyl, p-halo-benzyl or p-nitro-benzyl; R.sup.2 is ##STR3## R.sup.3 is ##STR4## R.sup.3a, R.sup.3b, R.sup.3c and R.sup.3d are independently hydrogen, C.sub.1 -C.sub.12 alkyl, C.sub.2 -C.sub.12 alkynyl, C.sub.1 -C.sub.12 alkoxy, C.sub.1 -C.sub.12 alkylthio, halo, --O--(CH.sub.2).sub.m --[O--(CH.sub.2).sub.n ].sub.p --O--(C.sub.1 -C.sub.12 alkyl) or --O--(CH.sub.2).sub.q --X--R.sup.4 ; m is 2, 3 or 4; n is 2, 3 or 4; p is 0 or 1; q is 2, 3 or 4; X is pyrrolidino, piperidino or piperazino; and R.sup.4 is hydrogen, C.sub.1 -C.sub.12 alkyl, C.sub.3 -C.sub.12 cycloalkyl, benzyl or C.sub.3 -C.sub.12 cycloalkylmethyl; with the proviso that at least one of R.sup.z1 and R.sup.z2 must be hydrogen; or a pharmaceutically acceptable salt thereof.