The knowledge of damage levels is vital to define protection schemes, beam loss monitor thresholds, safe beam limits for setting up the machines, etc. This talk will try to revisit our present knowledge and assumptions on damage levels in the LHC in terms of lost beam intensity, beam momentum and emittance. It is clear that with the LHC's unprecedented energy reach, benchmark tests to cross-check energy deposition simulations for all possible energies before LHC start-up have not been possible. Also, the definition of when equipment is damaged is not always straight forward. In view of the obvious limitations to our knowledge of damage levels, operational commissioning and LHC running strategies will be re-discussed, open questions will be highlighted and proposals will be presented where possible.

The influence of positions 11 and 24 on hypocalcaemic potency and duration of action was examined. These positions are respectively occupied by threonine and glutamine in HCT, but by the basic amino acids lysine and arginine in SCT. Replacement of threonine by lysine trebled the hypocalcaemic potency of HCT and slightly prolonged its duration of action. Substitution of arginine for glutamine reduced the activity to about one tenth. The simultaneous introduction of both basic amino acids yielded an analogue intermediate in activity between those obtained by the single substitutions. The analogue [Bmp1, Va18, Lys11, Arg24]-HCT displayed the same effects as [Lys11]-HCT.

Relative activities of a series of corticotrophin analogues have been measured by means of five different bioassays using the rat. Similarities in the relative potencies of various ACTH analogues determined using lipolysis or steroidogenesis in vivo and for the lipolytic and steroidogenic responses of fat pads and adrenal slices in vitro emerged and support the concept of a close structural relationship between the ACTH receptors in adipose and adrenal tissues in the rat. Potencies based on the steroidogenic response of isolated adrenal cells, adrenal slices or in-vivo experiments differed markedly from each other. Inactivation of peptides did not occur in the isolated cell assay, so it is likely that this assay estimates potency at the receptor level. A number of arguments suggest that the difference between the isolated cell assay and the other steroidogenic assays lies solely in the effects of peptide inactivation in the latter, and this allows the relative metabolic stabilities for the peptide analogues in these assays to be calculated. In this way it can be shown that: (1) Replacement of L-Ser by D-Ser in amino acid position 1 markedly increases the metabolic stability of the peptide and has only a slight effect on receptor properties. (2) Shortening at the NH2-terminus reduces the activity of peptides at the receptor level by several orders of magnitude, but increases their relative metabolic stability. (3) Introduction of amide groups at the CO2H-terminus markedly increases receptor potency of (1-16), (1-17) and (1-18) ACTH without affecting their metabolic stability in vivo. However, amidation of the CO2H-terminus does have a large effect on metabolic stability in the adrenal slice assay. (4) Replacement of Arg by Lys in positions 17 and 18 of (1-18) ACTH increases potency at the receptor level (adrenal cells) but has little effect on metabolic stability. The comparison of potencies obtained in the various assays, therefore, throws light on the significance of each assay. In addition, the effects of structural modification of analogues can be separately evaluated with respect to the metabolic stability of a peptide and its potency at the receptor level.

Assays of 8 synthetic analogues of human calcitonin in rats showed that their hypocalcaemic activity was drastically reduced by deletion of the C-terminal amide group, chain-shortening or opening of the disulphide ring, but unaffected or enhanced by modification of the N-terminal amino group.

Assays of 8 synthetic analogues of human calcitonin in rats showed that their hypocalcaemic activity was drastically reduced by deletion of the C-terminal amide group, chain-shortening or opening of the disulphide ring, but unaffected or enhanced by modification of the N-terminal amino group.

AbstractIn stufenweisem Aufbau werden die Teilsequenzen (I), (II), (IV) und (VI) dargestellt.

AbstractA detailed account is given of the total synthesis of human calcitonin M, the hypocalcaemic hormone possessing the dotriacontapeptide sequence I. In the build up of I, the protected sequences 1–10 and 11–32 served as intermediates for the preparation of the protected precursor dotriacontapeptide 1–32 (II). While the synthesis of the fragment 1–10 has been reported previously [1], the present account includes a detailed description of the build up of the intermediate 11–32. Racemisation encountered in the synthesis of this fragment is discussed and conditions indicated in which it is minimized.From the final coupling step using dicyclohexylcarbodiimide‐N‐hydroxysuccinimide [3], the protected dotriacontapeptide II was obtained pure in a yield of 65% after counter‐current distribution.In the removal by acidolysis of the protecting groups from II even under optimal conditions two side reactions occur: alkylation of the 8‐methionine side chain and N to O acyl migration at the serine or threonine residues. By‐products from these reactions were removed by counter‐current distribution giving very pure I free of diastereoisomers and possessing the biological activity of highly purified natural calcitonin M. In the routine assay [4] after repeated testing its activity was evaluated at 100 ± 5 U/mg (calculated on content of free peptide).

Research Article| February 01 1969 Structure and synthesis of human calcitonin M B. Riniker; B. Riniker 1Research Laboratories, Pharmaceutical Department, CIBA Limited, Basle, Switzerland Search for other works by this author on: This Site PubMed Google Scholar M. Brugger; M. Brugger 1Research Laboratories, Pharmaceutical Department, CIBA Limited, Basle, Switzerland Search for other works by this author on: This Site PubMed Google Scholar B. Kamber; B. Kamber 1Research Laboratories, Pharmaceutical Department, CIBA Limited, Basle, Switzerland Search for other works by this author on: This Site PubMed Google Scholar W. Rittel; W. Rittel 1Research Laboratories, Pharmaceutical Department, CIBA Limited, Basle, Switzerland Search for other works by this author on: This Site PubMed Google Scholar P. Sieber; P. Sieber 1Research Laboratories, Pharmaceutical Department, CIBA Limited, Basle, Switzerland Search for other works by this author on: This Site PubMed Google Scholar R. Neher R. Neher 1Research Laboratories, Pharmaceutical Department, CIBA Limited, Basle, Switzerland Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1969) 111 (3): 14P. https://doi.org/10.1042/bj1110014Pa Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation B. Riniker, M. Brugger, B. Kamber, W. Rittel, P. Sieber, R. Neher; Structure and synthesis of human calcitonin M. Biochem J 1 February 1969; 111 (3): 14P. doi: https://doi.org/10.1042/bj1110014Pa Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu nav search search input Search input auto suggest search filter All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1969 The Biochemical Society1969 Article PDF first page preview Close Modal You do not currently have access to this content.

AbstractThe total synthesis of the hypocalcaemic hormone α‐thyrocalcitonin (I) isolated from porcine thyroid glands is reported in detail. By the fragment condensation approach, using coupling procedures known to avoid racemisation, the fully protected dotriacontapeptide sequence II was synthesised. In the build up of II the disulfide ring bridge connecting the cysteine residues 1 and 7 was preformed in the protected nonapeptide fragment 1–9. Simultaneous removal by acidolysis of the nine protecting groups present in II yielded synthetic α‐thyrocalcitonin (I) in a state of high purity and possessing full biological activity; the disulfide bond remained intact during the de‐protection step. On repeated biological assay the synthetic preparation I in the test system of KUMAR et al. [2] was found to possess an activity of 130.8 U/mg peptide.

Research Articles| May 27 2008 Synthetic Polypeptides Related to Corticotrophin Acting as Histamine Liberators Subject Area: Pharmacology R. Jaques; R. Jaques Research Laboratories of the Pharmaceutical Department of CIBA Ltd., Basle Search for other works by this author on: This Site PubMed Google Scholar M. Brugger M. Brugger Research Laboratories of the Pharmaceutical Department of CIBA Ltd., Basle Search for other works by this author on: This Site PubMed Google Scholar Pharmacology (1969) 2 (6): 361–370. https://doi.org/10.1159/000136040 Article history Received: March 16 1969 Published Online: May 27 2008 Content Tools Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation R. Jaques, M. Brugger; Synthetic Polypeptides Related to Corticotrophin Acting as Histamine Liberators. Pharmacology 1 June 1969; 2 (6): 361–370. https://doi.org/10.1159/000136040 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsPharmacology Search Advanced Search Article PDF first page preview Close Modal Keywords: Histamine liberation, Corticotrophin alkyl derivatives, Compound 48/80, Rat peritoneum This content is only available via PDF. 1969Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. You do not currently have access to this content.

A preliminary account is giver of the synthesis of calcitonin M (I), isolated from human C-cell tumour tissue [2] [3]. Identity of the synthetic and the natural hormone was established by thin-layer chromatography, thin-layer electrophoresis and conversion to oxidation products, as well as by reference to the pattern of tryptic degradation and by comparing the biological activity of the two hormones. The findings also afforded additional confirmation of the results of structural elucidation [1]. In the synthesis of I, use was made of methods described previously [4] for the preparation of porcine α-thyrocalcitonin, and also of a new method [5] which easily permits the formation of cyclic cystine peptides.

AbstractA synthesis of the dotriacontapeptide sequence I, reported by Neher et al. [1] for porcine α‐thyrocalcitonin (α‐TC), is described. The synthetic peptide is shown to be identical with α‐TC by thin layer chromatography and electrophoresis, by the pattern of trypsin degradation, and by its biological activity. Oxidation with hydrogen peroxide gave the methionine25 sulfoxide derivative, which was identical with α‐TC‐sulfoxide (formerly called β‐thyrocalcitonin) from pig thyroids.

Mild treatment of the methyl ester of (+)‐N α ‐(γ‐chlorobutyry1)‐L‐tryptophane with silver tetrafluoroborate gives a high yield of a crystalline iminolactone derivative. This compound is a useful intermediate in preparing (+)‐Nα‐methyl‐L‐tryptophane ((+)‐abrine).