Somatostatin analogs which define the role of the lysine-9 amino group
Structure‐activity studies of the lysine residue in the highly active cyclic hexapeptide somatostatin analog cyclo(Pro‐Phe‐D‐Trp‐Lys‐Thr‐Phe) confirm the importance of the lysine amino group for biological activity through the loss of activity seen on replacement of lysine by ornithine, arginine, hi...
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| Veröffentlicht in: | International Journal of Peptide and Protein Research 1983-01, Vol.21 (1), p.66-73 |
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| container_title | International Journal of Peptide and Protein Research |
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| creator | NUTT, RUTH F. VEBER, DANIEL F. CURLEY, PAUL E. SAPERSTEIN, RICHARD HIRSCHMANN, RALPH |
| description | Structure‐activity studies of the lysine residue in the highly active cyclic hexapeptide somatostatin analog cyclo(Pro‐Phe‐D‐Trp‐Lys‐Thr‐Phe) confirm the importance of the lysine amino group for biological activity through the loss of activity seen on replacement of lysine by ornithine, arginine, histidine and p‐amino phenylalanine. Three analogs containing thialysine, γ‐ and δ‐fluorolysine were equipotent to the parent as inhibitors of insulin, glucagon, and growth hormone release. The pKa's of the amino groups in these equiactive peptides ranged from 8.23–9.4. The lack of a correlation between the basicity of the amino groups and the biological activities suggests that deprotonation is not required for biological activity. |
| doi_str_mv | 10.1111/j.1399-3011.1983.tb03079.x |
| format | Article |
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Three analogs containing thialysine, γ‐ and δ‐fluorolysine were equipotent to the parent as inhibitors of insulin, glucagon, and growth hormone release. The pKa's of the amino groups in these equiactive peptides ranged from 8.23–9.4. 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Three analogs containing thialysine, γ‐ and δ‐fluorolysine were equipotent to the parent as inhibitors of insulin, glucagon, and growth hormone release. The pKa's of the amino groups in these equiactive peptides ranged from 8.23–9.4. The lack of a correlation between the basicity of the amino groups and the biological activities suggests that deprotonation is not required for biological activity.</description><subject>Biological Assay</subject><subject>Circular Dichroism</subject><subject>conformation</subject><subject>cyclic hexapeptide</subject><subject>hormone release inhibition</subject><subject>Hormones</subject><subject>Lysine</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>pKa</subject><subject>somatostatin</subject><subject>Somatostatin - analogs & derivatives</subject><subject>somatostatin analogs</subject><subject>structure activity relationships</subject><subject>Structure-Activity Relationship</subject><issn>0367-8377</issn><issn>1399-3011</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1983</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkE9PwjAYhxujQUQ_gsniwdtmu3frHw8mCgImRg9o9NaUrYPhtuK6Bfj2brJwNfbSpr_f-zR9ELoi2CPNull5BIRwARPiEcHBq-YYMBPe9gj1D9Ex6mOgzOXA2Ck6s3aFMQTA_B7qUQIEB2EfjWcmV5WxlarSwlGFyszCOptlGi2dWCdpoZ1qqZ3SZNoxye8529nm2hWOytPCOIvS1OtzdJKozOqLbh-g9_Hj23DqPr9Onob3z24UAKduDGxOfOrHERcJZSr2KdMB8xmmESeYKoH9hIYYwlhwTTAXnFNFolAEzbdoAgN0veeuS_Nda1vJPLWRzjJVaFNbyTHwIBTizyIJw4BTDE3xdl-MSmNtqRO5LtNclTtJsGxty5VslcpWqWxty8623DbDl90r9TzX8WG009vkd_t8k2Z69w-yHD6MRpQ2AHcPSG2ltweAKr8kZcBC-fEykbPJlIw4ofITfgBE7JwF</recordid><startdate>198301</startdate><enddate>198301</enddate><creator>NUTT, RUTH F.</creator><creator>VEBER, DANIEL F.</creator><creator>CURLEY, PAUL E.</creator><creator>SAPERSTEIN, RICHARD</creator><creator>HIRSCHMANN, RALPH</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>198301</creationdate><title>Somatostatin analogs which define the role of the lysine-9 amino group</title><author>NUTT, RUTH F. ; VEBER, DANIEL F. ; CURLEY, PAUL E. ; SAPERSTEIN, RICHARD ; HIRSCHMANN, RALPH</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4386-d37b1262dc89f67ad267e472706c8106a902f65035d98e1089886a1c5941396f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1983</creationdate><topic>Biological Assay</topic><topic>Circular Dichroism</topic><topic>conformation</topic><topic>cyclic hexapeptide</topic><topic>hormone release inhibition</topic><topic>Hormones</topic><topic>Lysine</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>pKa</topic><topic>somatostatin</topic><topic>Somatostatin - analogs & derivatives</topic><topic>somatostatin analogs</topic><topic>structure activity relationships</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>NUTT, RUTH F.</creatorcontrib><creatorcontrib>VEBER, DANIEL F.</creatorcontrib><creatorcontrib>CURLEY, PAUL E.</creatorcontrib><creatorcontrib>SAPERSTEIN, RICHARD</creatorcontrib><creatorcontrib>HIRSCHMANN, RALPH</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>International Journal of Peptide and Protein Research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>NUTT, RUTH F.</au><au>VEBER, DANIEL F.</au><au>CURLEY, PAUL E.</au><au>SAPERSTEIN, RICHARD</au><au>HIRSCHMANN, RALPH</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Somatostatin analogs which define the role of the lysine-9 amino group</atitle><jtitle>International Journal of Peptide and Protein Research</jtitle><addtitle>Int J Pept Protein Res</addtitle><date>1983-01</date><risdate>1983</risdate><volume>21</volume><issue>1</issue><spage>66</spage><epage>73</epage><pages>66-73</pages><issn>0367-8377</issn><eissn>1399-3011</eissn><abstract>Structure‐activity studies of the lysine residue in the highly active cyclic hexapeptide somatostatin analog cyclo(Pro‐Phe‐D‐Trp‐Lys‐Thr‐Phe) confirm the importance of the lysine amino group for biological activity through the loss of activity seen on replacement of lysine by ornithine, arginine, histidine and p‐amino phenylalanine. Three analogs containing thialysine, γ‐ and δ‐fluorolysine were equipotent to the parent as inhibitors of insulin, glucagon, and growth hormone release. The pKa's of the amino groups in these equiactive peptides ranged from 8.23–9.4. The lack of a correlation between the basicity of the amino groups and the biological activities suggests that deprotonation is not required for biological activity.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>6131045</pmid><doi>10.1111/j.1399-3011.1983.tb03079.x</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0367-8377 |
| ispartof | International Journal of Peptide and Protein Research, 1983-01, Vol.21 (1), p.66-73 |
| issn | 0367-8377 1399-3011 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_80384599 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Biological Assay Circular Dichroism conformation cyclic hexapeptide hormone release inhibition Hormones Lysine Magnetic Resonance Spectroscopy pKa somatostatin Somatostatin - analogs & derivatives somatostatin analogs structure activity relationships Structure-Activity Relationship |
| title | Somatostatin analogs which define the role of the lysine-9 amino group |
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