Johannes Meienhofer

Bio: Johannes Meienhofer is an academic researcher from Hoffmann-La Roche. The author has contributed to research in topics: Peptide synthesis & Peptide. The author has an hindex of 17, co-authored 39 publications receiving 1703 citations.

Solid-phase peptide synthesis using mild base cleavage of N alpha-fluorenylmethyloxycarbonylamino acids, exemplified by a synthesis of dihydrosomatostatin.

Abstract: N alpha-9-Fluorenylmethyloxycarbonyl (Fmoc) amino acids will be of advantage in solid phase peptide synthesis. The Fmoc-group is quantitatively cleaved by mild base (piperidine). This permits the use of tert-butyl-type side chain blocking and of peptide-to-resin linkage cleavable by mild acidolysis. Side reactions arising from repetitive acid deprotection and final HF cleavage in contemporary solid phase synthesis are avoided. Fully bioactive and homogeneous dihydrosomatostatin was obtained in 53% overall yield.

Solid phase synthesis without repetitive acidolysis. Preparation of leucyl-alanyl-glycyl-valine using 9-fluorenylmethyloxycarbonylamino acids.

Abstract: The utility of repetitive nonhydrolytic base cleavage of alpha-amino protective groups in solid phase peptide synthesis is shown by a preparation of the model tetrapeptide leucyl-alanyl-glycyl-valine on a p-benzyloxybenzyl ester polystyrene--1% divinylbenzene resin support. Nalpha-9-Fluorenylmethyloxycarbonyl (Fmoc: Carpino & Han, 1970, 1972) amino acids were coupled by the symmetrical anhydride procedure, followed by Fmoc group cleavage using 50% piperidine in methylene chloride. Quantitative removal of the Fmoc-tetrapeptide from the solid support was effected by treatment with 55% trifluoroacetic acid in methylene chloride. Homogeneous free tetrapeptide was obtained in 87% overall yield. The procedure is proposed to offer advantages over present solid phase methods which use acidolysis for repetitive alpha-amino group deblocking.

Rapid removal of protecting groups from peptides by catalytic transfer hydrogenation with 1,4-cyclohexadiene

Abstract: (6) H. Hagenmaier and M. Mutter, Tetrahedron Lett., 767-770 (1974). (7) W. Gohring and G. Jung, Justus Liebigs Ann. Chern., 1765-1789 (1975). (8) M. Mutter, R. Uhmann, and E. Bayer, Justus Liebigs Ann. Chern., 901-915 ( 1975). (9) G. Jung, G. Bovermann, W. Gohring, and G. Heusel in "Peptides: Chemistry, Structure and Biology," R. Walter and J. Meienhofer, Ed., Ann Arbor Sci. Publ., Ann Arbor, Mich., 1975, pp 433-437. (10) F A . Tjoeng, W Staines, S. St-Pierre, and R. S. Hodges, Biochirn. Biophys. Acta, 490, 489-496 (1977). (1975). (1 1) L. B. Smillie, PAABS Revista, 5, 183-263 (1976). (12) R. S. Hodges, J. Sodek, L. B. Smillie, and L. Jurasek, ColdSpring Harbor

PREPARATION AND PROPERTIES OF Nα‐9‐FLUORENYLMETHYLOXYCARBONYLAMINO ACIDS BEARING TERT.‐BUTYL SIDE CHAIN PROTECTION

Abstract: The preparation is described by several Nalpha-9-fluorenylmethyloxycarbonylamino acids and derivatives bearing tert.-butyl type side-chain protection of amine, carboxyl, guanido, hydroxyl, imidazol, and sulfhydryl functionalities. Physicochemical properties of these compounds have been determined. Cleavage of the Fmoc group by various amines appears to depend on the base strength and steric hindrance. Premature deblocking of Fmoc group by amine on solid support is very slow and may be negligible under the conditions of solid-phase synthesis.

Solid phase peptide synthesis utilizing 9‐fluorenylmethoxycarbonyl amino acids

Abstract: 9-Fluorenylmethoxycarbonyl (Fmoc) amino acids were first used for solid phase peptide synthesis a little more than a decade ago. Since that time, Fmoc solid phase peptide synthesis methodology has been greatly enhanced by the introduction of a variety of solid supports, linkages, and side chain protecting groups, as well as by increased understanding of solvation conditions. These advances have led to many impressive syntheses, such as those of biologically active and isotopically labeled peptides and small proteins. The great variety of conditions under which Fmoc solid phase peptide synthesis may be carried out represents a truly "orthogonal" scheme, and thus offers many unique opportunities for bioorganic chemistry.

Peptide nucleic acids

Abstract: A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker.

Identification of the major Abeta1-42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition.

Abstract: Alzheimer amyloid beta-peptide (Abeta) is a physiological peptide constantly anabolized and catabolized under normal conditions. We investigated the mechanism of catabolism by tracing multiple-radiolabeled synthetic peptide injected into rat hippocampus. The Abeta1-42 peptide underwent full degradation through limited proteolysis conducted by neutral endopeptidase (NEP) similar or identical to neprilysin as biochemically analyzed. Consistently, NEP inhibitor infusion resulted in both biochemical and pathological deposition of endogenous Abeta42 in brain. This NEP-catalyzed proteolysis therefore limits the rate of Abeta42 catabolism, up-regulation of which could reduce the risk of developing Alzheimer's disease by preventing Abeta accumulation.

Peptide-binding specificity of the molecular chaperone BiP.

Abstract: Members of the heat-shock protein family (hsp70s) can distinguish folded from unfolded proteins. This property is crucial to the role of hsp70s as molecular chaperones and is attributable to the amino-acid specificity of the peptide-binding site. The specificity for peptide ligands is investigated using a set of peptides of random sequence but defined chain length. The peptide-binding site selects for aliphatic residues and accommodates them in an environment energetically equivalent to the interior of a folded protein.

Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility

Abstract: A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than a corresponding DNA strand, and exhibit increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from a group consisting of naturally-occurring nucleobases and non-naturally-occurring nucleobases attached to a polyamide backbone, and contain C1-C8 alkylamine side chains. Methods of enhancing the solubility, binding affinity and sequence specificity of PNAs are provided.