Journal of Peptide Science J. Peptide Sci. 4: 101±110 (1998) Solution Conformation of an Immunogenic Peptide from HRV2: Comparison with the Conformation Found in a Complex With a Fab Fragment of an anti-HRV2 Neutralizing Antibody M. ANTO Á NIA MOLINS 1 *, MIQUEL A Á NGEL CONTRERAS 1 , IGNACIO FITA 2 and MIQUEL PONS 1 1 Departament de Quõ Âmica Orga Á nica, Universitat de Barcelona, Barcelona, Spain 2 Centre d'Investigacio  i Desenvolupament, Consejo Superior de Investigaciones Cientõ Âficas, Barcelona, Spain Received 6 May 1997 Accepted 26 May 1997 Abstract: The conformation of a [15]-peptide (H-VKAETRLNPDLQPTE-NH 2 ) from VP2 of rhinovirus HRV2 complexed with a Fab fragment was previously shown by X-ray crystallographic studies to be similar to the one found in the corresponding region of HRV1A. Antibodies raised against this peptide bind to and neutralize HRV2. In order to identify structural features preserved in solution that may explain the ability of this short peptide to mimic the structure of the protein surface, the peptide has been studied by NMR in aqueous solution as well as under denaturing conditions. The peptide is shown to be a random coil in solution. However, the sequence forming a 3 10 helix in the complex is biased into a helical conformation according to NOE intensity data as well as from urea and pH titrations. This sequence adopts the same conformation in an unrelated protein. NOE data suggest that a b- turn found in the complex may be sampled in solution. Also, Glu4, interacting with Arg6 in the crystal, has a reduced pK a value in solution. It is concluded that the local structure present in the random coil state of VP2(156±170) contains enough information to direct the production of antibodies that bind to and neutralize HRV2. # 1998 European Peptide Society and John Wiley & Sons, Ltd. Keywords: NMR; random coil; rhinovirus; synthetic vaccine INTRODUCTION Immunization with synthetic peptides has given rise to neutralizing antibodies for several viral diseases such as influenza [1], the common cold [2], foot-and- mouth disease [3] and AIDS [4, 5], as well as bacterial and parasitic diseases [6, 7]. These exam- ples suggest that, in spite of the expected high flexibility of short peptides, they may contain enough structural information to direct the recogni- tion of the cognate region in an intact protein on the surface of the pathogen. Abbreviations: ES-MS, electron spray mass spectrometry; HRV, human rhinovirus; MALDI-TOF-MS, matrix-assisted laser desorption and ionization-time of flight mass spectrometry; PDB, Protein Data Bank; TOCSY, total correlation spectroscopy; VP, Viral capsid protein. * Present address: Unitat de RMN, Serveis Cientõ Âfico-Te Ácnics, Universitat de Barcelona. Address for correspondence: Miquel Pons, Departament de Quõ Âmica Orga Á nica, Universitat de Barcelona, Martõ  Franque Ás, 1±11, E-08028, Barcelona, Spain # 1998 European Peptide Society and John Wiley & Sons, Ltd. CCC 1075-2617/98/020101-10