{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T06:39:13Z","timestamp":1792737553574,"version":"4.5.0"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"37","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,9,11]]},"abstract":"<jats:p>Collagen remodeling is an integral part of tissue development, maintenance, and regeneration, but excessive remodeling is associated with various pathologic conditions. The ability to target collagens undergoing remodeling could lead to new diagnostics and therapeutics as well as applications in regenerative medicine; however, such collagens are often degraded and denatured, making them difficult to target with conventional approaches. Here, we present caged collagen mimetic peptides (CMPs) that can be photo-triggered to fold into triple helix and bind to collagens denatured by heat or by matrix metalloproteinase (MMP) digestion. Peptide-binding assays indicate that the binding is primarily driven by stereo-selective triple-helical hybridization between monomeric CMPs of high triple-helical propensity and denatured collagen strands. Photo-triggered hybridization allows specific staining of collagen chains in protein gels as well as photo-patterning of collagen and gelatin substrates. In vivo experiments demonstrate that systemically delivered CMPs can bind to collagens in bones, as well as prominently in articular cartilages and tumors characterized by high MMP activity. We further show that CMP-based probes can detect abnormal bone growth activity in a mouse model of Marfan syndrome. This is an entirely new way to target the microenvironment of abnormal tissues and could lead to new opportunities for management of numerous pathologic conditions associated with collagen remodeling and high MMP activity.<\/jats:p>","DOI":"10.1073\/pnas.1209721109","type":"journal-article","created":{"date-parts":[[2012,8,27]],"date-time":"2012-08-27T23:18:09Z","timestamp":1346109489000},"page":"14767-14772","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":190,"title":["Targeting collagen strands by photo-triggered triple-helix hybridization"],"prefix":"10.1073","volume":"109","author":[{"given":"Yang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine A.","family":"Foss","sequence":"additional","affiliation":[{"name":"Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21231;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel D.","family":"Summerfield","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jefferson J.","family":"Doyle","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Collin M.","family":"Torok","sequence":"additional","affiliation":[{"name":"Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21231;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry C.","family":"Dietz","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205;"},{"name":"Division of Pediatric Cardiology, Department of Pediatrics, and Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin G.","family":"Pomper","sequence":"additional","affiliation":[{"name":"Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21231;"},{"name":"Institute for NanoBiotechnology, Johns Hopkins University, Baltimore, MD 21218"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Michael","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Johns Hopkins University, Baltimore, MD 21218;"},{"name":"Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218;"},{"name":"Institute for NanoBiotechnology, Johns Hopkins University, Baltimore, MD 21218"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,8,27]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"1371","article-title":"Novel anti-denatured collagen humanized antibody D93 inhibits angiogenesis and tumor growth: An extracellular matrix-based therapeutic approach","volume":"29","author":"Pernasetti F","year":"2006","unstructured":"F Pernasetti, et al., Novel anti-denatured collagen humanized antibody D93 inhibits angiogenesis and tumor growth: An extracellular matrix-based therapeutic approach. Int J Oncol 29, 1371\u20131379 (2006).","journal-title":"Int J Oncol"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1089\/02724570050198893"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-08-0538"},{"key":"e_1_3_3_4_2","first-page":"693","article-title":"Targeted therapy of cancer with radiolabeled antibodies","volume":"43","author":"Goldenberg DM","year":"2002","unstructured":"DM Goldenberg, Targeted therapy of cancer with radiolabeled antibodies. J Nucl Med 43, 693\u2013713 (2002).","journal-title":"J Nucl Med"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200700700"},{"key":"e_1_3_3_6_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/b103818","volume-title":"Collagen","author":"Engel J","year":"2005","unstructured":"J Engel, HP B\u00e4chinger Collagen, eds J Brinckmann, H Notbohm, PK M\u00fcller (Verlag Berlin Heidelberg, Springer), pp. 7\u201333 (2005)."},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1962210"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1039\/c1sm05329a"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0431915"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/bm701378k"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/bip.21536"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.77.032207.120833"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1039\/b919455j"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M605135200"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(02)03000-4"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol070238t"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2012.02.032"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp808690m"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200504529"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2009.05.030"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.1287"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201101163"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/bm800727z"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmat2203"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.03.064"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21222"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.03.015"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2470725"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/284067a0"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2010.11.076"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)65656-X"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2002.5439"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.12.7668"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/89126"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmat2116"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1201-1148"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118357"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012088562-6\/50024-8"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200420641"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M709885200"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0910312107"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1209721109","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T07:16:14Z","timestamp":1650006974000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1209721109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,8,27]]},"references-count":41,"journal-issue":{"issue":"37","published-print":{"date-parts":[[2012,9,11]]}},"alternative-id":["10.1073\/pnas.1209721109"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1209721109","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,8,27]]},"assertion":[{"value":"2012-08-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}