Abstract: Methods for obtaining N-terminal methionine-free proteins involve a novel E. coli methionine amino peptidase. The method is capable of in vitro or in vivo application. For in vivo application, a plasmid-borne DNA encoding the peptide is expressed in a bacterial host.

Abstract: A colony stimulating factor, CSF-1, is a lymphokine useful in overcoming the immunosuppression induced by chemotherapy or resulting from other causes. CSF-1 is obtained in usable amounts by recombinant methods, including cloning and expression of the murine and human DNA sequences encoding this protein.

Abstract: Bifunctional chemicals useful for linking aldehyde containing moieties to moieties containing functionalities which are or can be reactive with sulfhydryl are claimed and have the formula:L--S--(CH.sub.2).sub.n1 --CONH--SPACER--NH--Xwherein L is a leaving group selected from --H or --S--Ar, wherein Ar represents optionally substituted phenyl or pyridyl;n.sub.1 =2-4;X is selected from:--CO--Y--CONHNH.sub.2, a hydrazide; ##STR1## a hydrazine; ##STR2## a hydrazine; --CO--Y--NH--CONHNH.sub.2, a semicarbazide; and--CO--Z--NH--CSNHNH.sub.2, a thiosemicarbazide;wherein Y is alkylene or oxaalkylene and Z is alkylene or a polypeptide residue bridging the N-terminal amino group and C-terminal carboxy group thereof;the SPACER is oxaalkylene or oxaalkylene substituted with hydroxyl and specifically includes residues having formulas selected from--(CH.sub.2).sub.n2 --O--(CH.sub.2).sub.n2 --O--(CH.sub.2).sub.n2 --(a)wherein each n2 is independently 2-4 and ##STR3## wherein n3 is 2-6.

Abstract: A novel universal dominant selectable marker cassette is disclosed. The marker comprises the coding sequences for aminoglycoside phosphotransferase I (APH-I) which has been modified and truncated so as to render its use in recombinant vectors more convenient. The modified, truncated sequence (mtAPH-I) gene is capable, upon expression, of conferring resistance to a number of antibiotics on the host. One of these antibiotics, G418, is toxic to eucaryotic as well as procaryotic hosts. Also disclosed are methods of constructing fusion proteins having N-terminal sequences corresponding to a desired peptide sequence, and C-terminal sequences comprising the amino acids encoded by mtAPH-I.

Abstract: Two types of convenient portable control cassettes for the expression of protein encoding sequences in procaryotes are disclosed. Both cassettes comprise the P.sub.L promoter from lambda phage, which is controllable by means of a temperature sensitive repressor, operably linked to the ribosome binding site for N-gene (N.sub.RBS). In one embodiment, this cassette is bordered by restriction sites upstream of the P.sub.L promoter and immediately downstream from the N.sub.RBS permitting the insertion of a desired sequence containing its own start codon downstream from the cassette. The other embodiment contains an ATG start codon within the cassette and has a restriction site immediately 3' of the start codon.

Abstract: A method for controlling weight by suppressing the normal metabolism of adipose tissue is disclosed. Administration of tumor necrosis factor (TNF) or a pharmaceutical composition containing it results in suppression of anabolism of adipose cells.

Abstract: An improved magnetic particulate pigment suitable for use in recording media and media employing it are disclosed. The particles of the pigment comprise a magnetic core with an epitaxial layer containing approximately 0.05-2.0% of the total pigment as zinc ion. A process for preparing such particles is also disclosed.

Abstract: Human Tumor necrosis factor (TNF) has been prepared using recombinant methods. A human promyelocytic leukemia cell line has been induced using an improved induction procedure, and the TNF purified to homogeneity. Methods, vectors, and cells useful in obtaining human TNF in practical amounts are disclosed. Muteins having N-terminal deletions, which muteins have superior biological activity, are also disclosed.

Abstract: Human tumor necrosis factor (TNF) has been prepared using recombinant methods. A human promyelocytic leukemia cell line has been induced using an improved induction procedure, and the TNF purified to homogeneity. Methods, vectors, and cells useful in obtaining human TNF in practical amounts are disclosed. Muteins having N-terminal deletions, which muteins have superior biological activity, are also disclosed.

Abstract: An improved method for purifying TNF, especially recombinantly produced TNF in bacteria, is disclosed. The purification employs a hydrophobic support in a chromatographic column which is then developed, preferably by HPLC. Preliminary purifications using anion exchange resins are also helpful.

Abstract: An improved process for the isolation and purification of HIFNs is disclosed wherein a partially purified preparation of the HIFN is sequentially passed through an antibody affinity column and a reversed-phase high performance liquid chromatographic column. Organic solvents used during the elution are extracted and the protein concentrated for subsequent use.

Abstract: Novel compounds of the formula: ##STR1## and the pharmaceutically acceptable acid addition salts thereof, wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are each independently hydrogen, hydroxy, lower alkyl, lower alkoxy or halo;R is hydrogen or lower alkyl; andA is selected from the group consisting of:2-(benzodioxan-2-yl)-2-hydroxyethyl;.omega.-(benzodioxan-2-yl)-alkyl (1-4);3-(aryloxy)-2-hydroxypropyl, wherein aryloxy is phenyloxy optionally substituted by 1-3 moieties selected from the group consisting of lower alkyl, lower alkoxy, halo, alkylsulfamido, lower alkoxycarbonyl, cyano and trifluoromethyl;.omega.-arylalkyl (1-4), wherein aryl is phenyl optionally substituted by 1-3 moieties selected from the group consisting of lower alkyl, lower alkoxy, halo, alkylsulfamido, lower alkoxycarbonyl, cyano and trifluoromethyl;.omega.-aryl-.omega.-oxoalkyl (1-4), wherein aryl is as herein defined;.omega.-aryl-.omega.-hydroxyalkyl (1-4), wherein aryl is as herein defined; and.omega.

Abstract: Novel 5-aroyl-6-chloro- or 6-bromo-1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-7-carboxylic acids represented by the formula ##STR1## and the pharmaceutically acceptable, non-toxic esters and salts thereof, wherein Y is chloro or bromo and Ar is an optionally substituted phenyl, 2-furyl, or 2-thienyl ring or a 3-furyl, 3-thienyl, 2-pyrrolyl or 1-alkyl-2-pyrrolyl ring. These compounds are useful as anti-inflammatory, analgesic and antipyretic agents and as smooth muscle relaxants.

Abstract: Nonapeptide and decapeptide analogs of LHRH which have the formula: ##STR1## and the pharmaceutically acceptable salts thereof, wherein: X is a D-alanyl residue wherein one hydrogen on C-3 is replaced by:(a) a carbocyclic aryl-containing radical selected from the group consisting of phenyl substituted with three or more straight chain lower alkyl groups, naphthyl, anthryl, fluorenyl, phenanthryl, biphenylyl and benzhydryl; or(b) a saturated carbocyclic radical selected from the group consisting of cyclohexyl substituted with three or more straight chain lower alkyl groups, perhydronaphthyl, perhydrobiphenylyl, perhydro-2,2-diphenylmethyl, and adamantyl; or(c) a heterocyclic aryl containing radical selected from the group consisting of radicals represented by the following structural formulas: ##STR2## wherein A" and A' are independently selected from the group consisting of hydrogen, lower alkyl, chlorine, and bromine, and G is selected from the group consisting of oxygen, nitrogen, and sulfur;A is an aminoac

Abstract: Novel peptides of the formula: ##STR1## wherein: A, A' and A" are each independently Gly, D-Ala, D-Leu, or D-Trp, wherein A may optionally be N-alkylated or N-acylated;B is Pro, .DELTA..sup.3 -Pro, Thz, or diMeThz;C and C' are each independently Thr, Ser, Val, or alloThr;D is Glu, Gln, Asp, or Asn;R is hydrogen, or is lower alkyl or lower acyl, substituted for one of the hydrogens on the .epsilon.-amino group of the lysyl residue;X is Cys, Ala, ABU, or Cys(Me); andY is selected from the group consisting of hydroxy, Pro, Pro-Leu, and Pro-Leu-Met, -NH.sub.2, ProNH.sub.2, Pro-LeuNH.sub.2 and Pro-leu-MetNH.sub.2 ;and the pharmaceutically acceptable salts thereof, are useful for increasing immunologic competence. Methods for preparation of the peptides are also described.

Abstract: Nonapeptide and decapeptide analogs of LH-RH of the formula ##STR1## and the pharmaceutically acceptable salts thereof wherein: V is tryptophyl, phenylalanyl or 3-(1-naphthyl)-L-alanyl;W is tyrosyl, phenylalanyl or 3-(1-pentafluorophenyl)-L-alanyl;X is a D-amino acid residue of the formula: ##STR2## wherein R is a heterocyclic aryl containing radical selected from the group consisting of radicals represented by the following structural formulas: ##STR3## wherein A and A' are independently selected from the group consisting of hydrogen, lower alkyl, chlorine, and bromine, and G is selected from the group consisting of oxygen, nitrogen, and sulfur;Y is leucyl, isoleucyl, nor-leucyl or N-methyl-leucyl;Z is glycinamide or --NH--R.sup.1, wherein:R.sup.1 is lower alkyl, cycloalkyl, fluoro lower alkyl or ##STR4## wherein R.sup.2 is hydrogen or lower alkyl,are disclosed. These compounds exhibit potent LH-RH agonist properties.

Abstract: 2-(1,4-Benzodioxan-2-ylalkyl)imidazoles having the general formula ##STR1## wherein R.sup.1 and R.sup.2 are each independently selected from the group consisting of hydrogen, alkyl, optionally substituted phenyl, and optionally substituted phenyl lower alkyl;R.sup.3 is hydrogen, alkyl, or optionally substituted phenyl lower alkyl;n is an integer equal to 0, 1 or 2;with the proviso that R.sup.1, R.sup.2 and R.sup.3 cannot all be hydrogen and/or alkyl; and the pharmaceutically acceptable acid addition salts thereof, are useful as antidepressants.

Abstract: 2-(1,4-Benzodioxan-2-ylalkyl)imidazoles having the general formula: ##STR1## wherein R.sup.1, and R.sup.2 and R.sup.3 are independently selected from the group consisting of hydrogen, and alkyl, and wherein n is an integer equal to 0, 1 or 2, and the pharmaceutically acceptable acid addition salts thereof, are useful as antidepressants.

Abstract: Compounds of the formula ##STR1## and the pharmaceutically acceptable, non-toxic salts thereof, wherein: R is hydrogen, lower alkyl, or benzyl;X is a substitution for hydrogen at any position in the benzene ring and is selected from the group consisting of lower alkyl, lower alkoxyl, benzyl and halo;m is an integer from 0 to 4; andn is an integer from 0 to 2;are novel. These compounds have been shown to be .alpha..sub.2 blockers, and are, therefore, anti-depressants.

Abstract: 4,5-Dihydro-2-lower alkoxycarbonylamino-4-phenyl imidazoles and substituted phenyl derivatives thereof lower the blood pressure in a human being when administered at low doses.