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However, the design of such peptides is important for obtaining biomimetic small systems of metalloenyzmes as well as for the development of artificial systems. With this in mind, a cyclic decapeptide, C\u2010Asp, which contained three His residues and one Asp residue, and its linear derivative, O\u2010Asp, were synthesized. The C\u2010Asp peptide has two Pro\uf8ffGly \u03b2\u2010turn\u2010inducer units and, as a result of cyclization, and as shown by CD spectroscopy, its backbone is constrained into a more defined conformation than O\u2010Asp, which is linear and contains a single Pro\uf8ffGly unit. A detailed potentiometric, mass spectrometric, and spectroscopic study (UV\/Vis, CD, and EPR spectroscopy) showed that at a 1:1 Cu<jats:sup>2+<\/jats:sup>\/peptide ratio, both peptides formed a major [CuHL]<jats:sup>2+<\/jats:sup> species in the pH range 5.0\u20137.5 (C\u2010Asp) and 5.5\u20137.0 (O\u2010Asp). The corrected stability constants of the protonated species (log\u2009<jats:italic>K<\/jats:italic>*<jats:sub>CuH(O\u2212Asp)<\/jats:sub>=9.28 and log\u2009<jats:italic>K<\/jats:italic>*<jats:sub>CuH(C\u2212Asp)<\/jats:sub>=10.79) indicate that the cyclic peptide binds Cu<jats:sup>2+<\/jats:sup> ions with higher affinity. In addition, the calculated value of <jats:italic>K<\/jats:italic><jats:sub>eff<\/jats:sub> shows that this higher affinity for Cu<jats:sup>2+<\/jats:sup> ions prevails at all pH values, not only for a 1:1 ratio but even for a 2:1 ratio. The spectroscopic data of both [CuHL]<jats:sup>2+<\/jats:sup> species are consistent with the exclusive coordination of Cu<jats:sup>2+<\/jats:sup> ions by the side\u2010chain functionalities of the three His residues and the Asp residue in a square\u2010planar or square\u2010pyramidal geometry. Nonetheless, although these data show that, upon metal coordination, both peptides adopt a similar fold, the larger conformational constraints that are present in the cyclic scaffold results in different behaviour for both [CuHL]<jats:sup>2+<\/jats:sup> species. CD and NMR analysis revealed the formation of a more rigid structure and a slower Cu<jats:sup>2+<\/jats:sup>\u2010exchange rate for [CuH(C\u2010Asp)]<jats:sup>2+<\/jats:sup> compared to [CuH(O\u2010Asp]<jats:sup>2+<\/jats:sup>. This detailed comparative study shows that cyclization has a remarkable effect on the Cu<jats:sup>2+<\/jats:sup>\u2010coordination properties of the C\u2010Asp peptide, which binds Cu<jats:sup>2+<\/jats:sup> ions with higher affinity at all pH values, stabilizes the [CuHL]<jats:sup>2+<\/jats:sup> species in a wider pH range, and has a slower Cu<jats:sup>2+<\/jats:sup>\u2010exchange rate compared to O\u2010Asp.<\/jats:p>","DOI":"10.1002\/chem.201203545","type":"journal-article","created":{"date-parts":[[2013,1,4]],"date-time":"2013-01-04T11:40:35Z","timestamp":1357299635000},"page":"2076-2088","source":"Crossref","is-referenced-by-count":36,"title":["Harnessing the Flexibility of Peptidic Scaffolds to Control their Copper(II)\u2010Coordination Properties: A Potentiometric and Spectroscopic Study"],"prefix":"10.1002","volume":"19","author":[{"given":"Ana","family":"Fragoso","sequence":"first","affiliation":[]},{"given":"Pedro","family":"Lamosa","sequence":"additional","affiliation":[]},{"given":"Rita","family":"Delgado","sequence":"additional","affiliation":[]},{"given":"Olga","family":"Iranzo","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2013,1,4]]},"reference":[{"key":"e_1_2_6_1_2","unstructured":"\u00a0"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0010-8545(98)00261-6"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1039\/B607515K"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.04.027"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1039\/B813398K"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.07.004"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3011.1999.00139.x"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1039\/b811452h"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.58"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030739"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr00050a003"},{"key":"e_1_2_6_12_2","unstructured":"\u00a0"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2010.11.011"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1039\/c2dt31224g"},{"key":"e_1_2_6_15_2","unstructured":"\u00a0"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr9500390"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr040410w"},{"key":"e_1_2_6_18_2","unstructured":"\u00a0"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/1439-7633(20010601)2:6<432::AID-CBIC432>3.0.CO;2-6"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/psc.964"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar700259k"},{"key":"e_1_2_6_22_2","unstructured":"\u00a0"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/bip.360370607"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-1693(03)00492-4"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2005.06.040"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/ic060430b"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2008.03.058"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/psc.1037"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200800677"},{"key":"e_1_2_6_29_3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200800677"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.200900636"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja106206z"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1039\/c0ob01072c"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0282(199609)39:3<297::AID-BIP3>3.0.CO;2-J"},{"key":"e_1_2_6_34_2","unstructured":"\u00a0"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-3757(19981102)110:21<3160::AID-ANGE3160>3.0.CO;2-J"},{"key":"e_1_2_6_35_3","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-3773(19981116)37:21<2990::AID-ANIE2990>3.0.CO;2-#"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1039\/B315489K"},{"key":"e_1_2_6_37_2","unstructured":"L.\u2005D. 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