Abstract: Molecular structures of .beta.-adrenergic antagonists are modified to produce biologically active compounds. The .beta.-antagonists are modified to form molecules of the general structure: ##STR1## wherein R is most generally R"--OCH.sub.2 --, and in some instances is R"--, and R"=an aryl or substituted aryl moiety; R'=--H, --CH.sub.3, or a short chain alkyl moiety; and Y=--OH, or more usually, --OAX or --NHAX, where A=an alkyl, aryl, or aralkyl moiety, and X=a terminal grouping, such as --CH.sub.3, --CF.sub.3 or --(CH.sub.2).sub.n COOH; or AX may be a carrier moiety consisting of a defined peptide or protein.

Abstract: Molecular structures of .beta.-adrenergic antagonists are modified to produce biologically active compounds. The .beta.-antagonists are modified to form molecules of the general structure: ##STR1## wherein R is most generally R"--OCH.sub.2 --, and in some instances is R"--, and R"=an aryl or substituted aryl moiety; R'=--H, --CH.sub.3, or a short chain alkyl moiety; and Y=--OH, or more usually, --OAX or --NHAX, where A=an alkyl, aryl, or aralkyl moiety, and X=a terminal grouping, such as --CH.sub.3, --CF.sub.3 or --(CH.sub.2).sub.n COOH; or AX may be a carrier moiety consisting of a defined peptide or protein.

Abstract: Biologically active drugs, e.g. catecholamine hormones, are coupled to carrier molecules, e.g. monodisperse peptides to produce conjugate molecules. The conjugate molecules retain biological activity, but the pharmacokinetic, pharmacodynamic and/or potency properties of the drug is modified. The drug is coupled to the carrier via a spacer moiety which not only serves to covalently link the drug to the carrier, but also insulates the biologically active portion of the drug, i.e., the pharmacophore, from degradation during the coupling process. The carrier preferably consists of a monodisperse peptide in which the sequence of amino acid residues is carefully preselected and controlled.

Abstract: Compounds of the formula: ##STR1## wherein n is 0 or 1, R is lower alkyl (substituted or unsubstituted), R' is H or lower alkyl, and R" is a branched alkyl, alkyl-cycloalkyl, cycloalkyl, polycycloalkyl (poly=2 or more, fused or non-fused), phenyl or alkyl-substituted phenyl, and physiologically acceptable cationic and acid addition salts thereof, which compounds are potent sweeteners. These derivatives of gem-diaminoalkanes are many times sweeter than sugar and are free from undesirable flavor qualities. Furthermore, they possess an unanticipated high degree of solubility compared with known synthetic sweeteners. In addition, the compounds possess high stability so that they can be used in all types of beverages and in conventional food processing. Sweetening compositions and sweetened edible compositions of these compounds are also provided.

Abstract: An apparatus for synthesizing a polypeptide chain on an insoluble solid support in a continuous flow reactor by performing a series of stepwise coupling reactions under high pressure is disclosed. A deprotecting agent reservoir, a solvent reservoir, a neutralizing solution reservoir, and a plurality of amino acid reservoirs are provided. Each reservoir can be selectively coupled to the reactor and a source of high pressure inert gas or an appropriate pump can be used to force the fluids as needed to the reactor. The reactor also includes a recycle loop whereby the amino acid from a particular reservoir can be recycled through the reactor under high pressure.

Abstract: In the synthesis of a polypeptide chain wherein an N.sup..alpha. -urethane-protected amino acid mixed anhydride is coupled with an amino-unprotected second amino acid, the improvement comprising conducting said coupling at room temperature or above. This method provides rapid, essentially quantitative reactions without the necessity for reduced temperatures. The method is particularly useful in the solid-phase synthesis of peptides where shortened coupling cycles and improved yields of substantially pure products are obtained.

Abstract: Biologically active derivatives of norepinephrine are disclosed. Such derivatives are catecholamines wherein isoproterenol is modified by extending the isopropyl functional grouping to an alkyl, aryl, or alkyl-aryl chain of variable length where said chain terminates in a carboxylic acid functional group, or in a substituted amide functional group. Such derivatives are .beta.-adrenergic and a number of such derivatives e.g., 6-(.beta.-3,4-dihydroxyphenyl-.beta.-hydroxy)-ethylamino heptanoic acid p-toluide, 6-(.beta.-3,4-dihydroxyphenyl-.beta.-hydroxy)-ethylamino heptanoic acid para-n-butyl anilide; 6-(.beta.,3,4-dihydroxyphenyl-.beta.-hydroxy)-ethylamino heptanoic acid para-methoxy anilide; 6-(.beta.-3,4-dihydroxyphenyl-.beta.-hydroxy)-ethylamino heptanoic acid paratrifluoromethyl anilide; and 6-(.beta.-3,4-dihydroxyphenyl-.beta.-hydroxy)-ethylamino heptanoic acid N-methyl para-toluide display a .beta.-adrenergic activity at least several orders of magnitude greater than isoproterenol itself.

Abstract: In the method for the synthesis of a polypeptide chain on an insoluble solid support wherein an amino acid is introduced into a reactor packed with an insoluble solid support containing substituent groups reactive with said amino acid, coupling said amino acid to said support by condensation reaction with said reactive substituent groups, introducing a second similar or dissimilar amino acid into said reactor and coupling said second amino acid to said first amino acid and repeating the process until the desired polypeptide is obtained, the improvement wherein a high pressure flow system is used and the reaction pressure in said reactor during said synthesis is at least 200 psi up to 10,000 psi or more, in order to obtain rapid reactions and quantitative yields of the desired products.

Abstract: Homopolymers and copolymers containing the amino acid 3,4-dihydroxy-L-phenylalanine (dopa) have been prepared via the synthesis of a protected N-carboxyanhydride (NCA) of the amino acid. These dopa-containing polymers have many uses as in the treatment of Parkinsonism, as drug delivery systems, antioxidants, and fibers and in the production of non-thrombogenic substrates.

Abstract: Water-soluble copolypeptides having high physiological activity for prolonged periods of time comprise water-soluble, linear copolypeptides having attached to their polymeric backbone at least one substituent having the structure: ##STR1## wherein Z is an aromatic group derived from a physiologically active compound and x is an integer and equal to 0 or 1.