Abstract: Nucleic acid hybridization probes are provided which comprise an N.sup.4 -(substituted amino)cytosine moiety, wherein the substituted amino group comprises a tag moiety, whereby the probe is detected. Methods of preparing probes of the invention, intermediates used in such methods, and methods of using the probes of the invention in hybridization assays are also provided. Typical tag moieties employed with the probes of the invention are biotinyl, aminothiadiazole and fluorescein derivatives, connected to N.sup.4 -amino groups of modified cytosines of the probe through linker moieties. Probes tagged with biotin are typically detected by binding to the biotinyl moieties, through a streptavidin or avidin molecule, a reporter group which includes streptavidin or avidin and then detecting a signal due to the reporter group.

Abstract: Fluorescent linker moieties are provided which comprise a fluorescent compound such as fluorescein attached to a linker moiety such that a functional group of the linker is available for attachment to an affinity molecule such as a nucleic acid which has an N.sup.4 (substituted amino) cytosine moiety. Probes tagged with fluorescent derivatives such as fluorescein, tetramethyrhodamine or tetraethylrhodamine may be detected by fluorescence spectroscopic methods.

Abstract: Novel, biologically active, 28-amino acid analogs of human vasoactive intestinal peptide are provided.

Abstract: Novel biologically active vasoactive intestinal peptide (VIP) analogues are provided.

Abstract: Nucleic acid hybridization probes are provided which comprise an N.sup.4 -(substituted amino)cytosine moiety, wherein the substituted amino group comprises a tag moiety, whereby the probe is detected. Methods of preparing probes of the invention, intermediates used in such methods, and methods of using the probes of the invention in hybridization assays are also provided. Typical tag moieties employed with the probes of the invention are biotinyl, aminothiadiazole and fluorescein derivatives, connected to N.sup.4 -amino groups of modified cytosines of the probe through linker moieties. Probes tagged with biotin are typically detected by binding to the biotinyl moieties, through a streptavidin or avidin molecule, a reporter group which includes streptavidin or avidin and then detecting a signal due to the reporter group.

Abstract: Nucleic acid hybridization probes are provided which comprise nucleoside bases or terminal nucleotide phosphates chemically linked to aromatic sulfonamide inhibitors of carbonic anhydrase. Methods of preparing probes of the invention, intermediates used in such methods, and methods of using the probes of the invention in hybridization assays are also provided. A probe of the invention is detected by binding to it a reporter group, such as a homopolymer or heteropolymer of enzymes, which includes a carbonic anhydrase which binds to the inhibitor linked to the probe, and then detecting the bound reporter group, as by production of a fluorescent or colored product in a reaction catalyzed by an enzyme component of the reporter group. Also provided are enzyme immunoassays wherein detection of antibody is by a process which comprises a chemical reaction catalyzed by a carbonic anhydrase.

Abstract: Reaction of a ketoxime-derivatized resin with a strong acid salt of aspartic anhydride or glutamic anhydride yields a novel aspartyl or glutamyl ketoxime ester-derivatized resin, wherein the aspartyl or glutamyl groups are esterified predominantly at the .alpha.-carboxyl group and wherein the aspartyl or glutamyl groups are not covalently protected at the amino group or the carboxyl group that is not esterified. Aminolysis in the presence of a weak acid of the novel aspartyl or glutamyl ketoxime ester-derivatized resin, wherein the aspartyl or glutamyl groups remain as the strong acid salt, with a salt of an amino acid with a base or an amino acid ester yields the corresponding dipeptide or dipeptide ester. After aminoylsis, the ketoxime-derivatized resin can be reused. An advantageous solid-phase method is thus provided for making .alpha.-L-aspartyl dipeptide ester sweeteners, including aspartame, and the immunopotentiating dipeptide, .alpha.-L-glutamyl-L-asparagine.

Abstract: Human pancreatic GRF and the hypothalamic GRFs for the human and several other mammalian species were earlier characterized and synthesized. The invention provides synthetic peptides which are potent stimulators of the release of pituitary GH in animals, including humans, and which have the formula: R.sub.1 -R.sub.2 R.sub.3 -Ala-R.sub.5 -R.sub.6 -R.sub.7 -R.sub.8 -R.sub.9 -R.sub.10 -R.sub.11 -R.sub.12 -R.sub.13 -Leu-R.sub.15 -Gln-Leu-R.sub.18 -R.sub.19 -R.sub.20 -R.sub.21 -Leu-Leu-Gln-Glu-R.sub.26 -R.sub.27 -R.sub.28 -Arg-Y wherein R.sub.1 is Tyr, D-Tyr, Met, Phe, D-Phe, Leu, His or D-His, which has either a C.sup.a Me or N.sup.a Me substitution or is unsubstituted; R.sub.2 is Ala or D-Ala; R.sub.3 is Asp or D-Asp; R.sub.5 is Ile or Leu; R.sub.6 is Phe or Tyr; R.sub.7 is Ser or Thr; R.sub.8 is Ser, Asn, Thr or Gln; R.sub.9 is Ala or Ser; R.sub.10 is Tyr, Phe or Leu; R.sub.11 in Arg, Orn or Lys; R.sub.12 is Arg, Orn or Lys; R.sub.13 is Ile, Leu, Phe or Val; R.sub. 15 is Gly or Ala; R.sub.18 is Ala or Ser; R.

Abstract: Compounds of the formula: ##STR1## wherein R.sub.1 is a moiety selected from the group consisting of ##STR2## R.sub.2 -R.sub.22 are amino acid moieties wherein R.sub.2 is an optional moiety which when present is selected from the group consisting of Ser and Gly,R.sub.8 is Leu or Val,R.sub.10 is Gln, Lys, or Gly,R.sub.11, R.sub.14, and R.sub.20 are each independently selected from the group consisting of Gln and Lys,R.sub.12 is Leu or Trp,R.sub.13 is Gln or Ser,R.sub.17 is Gln or His,R.sub.19 is Leu or Cys,R.sub.21 is Gln or Thr,R.sub.22 is an optional moiety which when present is selected from the group consisting of Leu and Tyr;R.sub.24 -R.sub.

Abstract: Reaction of a ketoxime-derivatized resin with a strong acid salt of aspartic anhydride or glutamic anhydride yields a novel aspartyl or glutamyl ketoxime ester-derivatized resin, wherein the aspartyl or glutamyl groups are esterified predominantly at the .alpha.-carboxyl group and wherein the aspartyl or glutamyl groups are not covalently protected at the amino group or the carboxyl group that is not esterified. Aminolysis in the presence of a weak acid of the novel aspartyl or glutamyl ketoxime ester-derivatized resin, wherein the aspartyl or glutamyl groups remain as the strong acid salt, with a salt of an amino acid with a base or an amino acid ester yields the corresponding dipeptide or dipeptide ester. After aminolysis, the ketoxime-derivatized resin can be reused. An advantageous solid-phase method is thus provided for making .alpha.-L-aspartyl dipeptide ester sweeteners, including aspartame, and the immunopotentiating dipeptide, .alpha.-L-glutamyl-L-asparagine.

Abstract: Compounds of the formula: ##STR1## wherein R.sub.1 is a moiety selected from the group consisting of ##STR2## R.sub.2 -R.sub.22 are amino acid moieties wherein R.sub.2 is an optional moiety which when present is selected from the group consisting of Ser and Gly,R.sub.8 is Leu, Val, or Ile,R.sub.10 is Gln, Lys, or Gly,R.sub.11, R.sub.14, and R.sub.20 are each independently selected from the group consisting of Gln and Lys,R.sub.12 is Leu or Trp,R.sub.13 is Gln or SerR.sub.17 is Gln or His,R.sub.21 is Gln or Thr,R.sub.

Abstract: This invention relates to the synthesis of steroids which are useful for their biological activity or which may be converted to steroids which have such activity. These syntheses include the steroid compounds and processes for their preparation.An object of the invention is to provide syntheses which are applicable to materials which are readily available in good supply for converting such materials to steroids which are useful and desirable in the manufacture of pharmaceutical products.More particularly, I have sought to discover processes and intermediate compounds useful in the synthesis of 24, 25-dihydroxycholesterol from hyodeoxycholic acid or lithocholic acid which are constituents of, and readily available from, animal bile.

Abstract: This invention relates to the synthesis of steroids which are useful for their biological activity or which may be converted to steroids which have such activity. More particularly, the invention pertains to the synthesis of 24,25-dihydroxycholesterol. It includes intermediate sterols of this synthesis and processes for their preparation.

Abstract: The synthesis of 1.alpha.,25-dihydroxycholesterol, 1.alpha.,25-dihydroxy-7-dehydrocholesterol and 1.alpha.,25-dihydroxycholecalciferol and other sterol derivatives from bile acids. Also the synthesis of 3,6-diketo steroids useful in the production of 1.alpha.,25-dihydroxycholesterol and other sterols which are biologically active or can be converted to biologically active sterols. The invention involves the sterols so produced and the processes by which they are prepared.

Abstract: The synthesis of 25-hydroxycholesterol and 1.alpha.,25-dihydroxycholesterol in which the sterol nucleus of an ester of hyodeoxycholic acid is stabilized by protection of the 3 and 6.alpha.-hydroxyl groups with alkyl groups, alkyl ether groups, preferably with the 3.beta.-methoxyethoxymethyl group or with the heterocyclic 2-tetrahydropyran group, then extending the chain from the carbon at the 24-position to a cyanide group at the 25-position and then subjecting the sterol so formed to a series of reactions by which it is transformed into 1.alpha.,25-dihydroxycholesterol or by a modified series of reactions to 25-hydroxycholesterol.

Abstract: The synthesis of 25-hydroxycholesterol and 25-hydroxycholecalciferol from animal bile starting materials in which hyodeoxycholic acid or an ester thereof is converted to the 3.beta.-hydroxy-5-cholenic acid alkyl ester, and this is converted to 3.beta.-hydroxy-25-cyano-5-cholene by a series of steps by which the sterol nucleus is stabilized by placing a protecting group at the 3 position and then extending the chain from the carbon at the 24 position to a cyanide group at the 25 position. The compound so formed is subjected to a series of reactions by which it is transformed into 25-hydroxy-7-dehydrocholesterol which may then be irradiated with ultraviolet light to 25-hydroxycholecalciferol. The invention discloses new and improved processes for preparing these end products and also new compounds formed as intermediates and processes for preparing these intermediates.

Abstract: In the synthesis of sterols wherein methoxyethoxymethyl groups in an ether linkage are attached to the nucleus of the sterol to protect the sterol nucleus during other steps of the synthesis and the sterols are thereafter treated to remove the methoxyethoxymethyl groups and set free the hydroxyl groups, the improvement in which the sterols being treated with zinc bromide are held in a methylene chloride solution containing a small amount of an aliphatic alcohol having from 1 to 6 carbon atoms.

Abstract: The synthesis of 1.alpha.,25-dihydroxycholesterol, 1.alpha.,25-dihydroxy-7-dehydrocholesterol and 1.alpha.,25-dihydroxycholecalciferol and other sterol derivatives from bile acids. Also the synthesis of 3,6-diketo steroids useful in the production of 1.alpha.,25-dihydroxycholesterol and other sterols which are biologically active or can be converted to biologically active sterols. The invention involves the sterols so produced and the processes by which they are prepared.

Abstract: The synthesis of 25-hydroxycholesterol from animal bile starting materials in which hyodeoxychloic acid or an ester thereof is converted to the 3.beta.-hydroxy-5-cholenic acid alkyl ester, and then converted to 3.beta.-hydroxy-25-cyano-5-cholene by a series of steps in which the sterol nucleus is stablized by use of a 3.alpha.,5.alpha.-bridge sometimes called an i-steroid configuration, and the carbon chain then extended from the carbon at the 24-position to a cyanide group at the 25-position. The compound so formed is subjected to a series of reactions by which it is transformed into 25-hydroxy-7-dehydrocholesterol which may then be irradiated with ultraviolet light to 25-hydroxycholecalciferol. The invention discloses new and improved processes for preparing these end products and also the compounds formed as intermediates and processes for preparing these intermediates.