(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization I International Bureau (10) International Publication Number (43) International Publication Date WO 2012/123419 Al 20 September 2012 (20.09.2012) P O P C T (51) International Patent Classification: (74) Common Representative: VIB VZW; Rijvisschestraat A61L 27/00 (2006.01) A61L 31/16 (2006.01) 120, B-9052 Gent (BE). C07K 14/00 (2006.01) C07K 14/40 (2006.01) (81) Designated States (unless otherwise indicated, for every A61L 31/08 (2006.01) kind of national protection available): AE, AG, AL, AM, (21) International Application Number: AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, PCT/EP2012/054285 CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, (22) International Filing Date: HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, 12 March 2012 (12.03.2012) KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, (25) Filing Language: English MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SC, SD, (26) Publication Language: English SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, (30) Priority Data: TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. 11157842.3 11 March 201 1 ( 11.03.201 1) EP (84) Designated States (unless otherwise indicated, for every 61/45 1,855 11 March 201 1 ( 11.03.201 1) US kind of regional protection available): ARIPO (BW, GH, 61/487,595 18 May 201 1 (18.05.201 1) us GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, 11176725.7 5 August 201 1 (05.08.201 1) EP UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, (71) Applicants (for all designated States except US): VIB TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, VZW [BE/BE]; Rijvisschestraat 120, B-9052 Gent (BE). DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, VRIJE UNIVERSITEIT BRUSSEL [BE/BE]; Pleinlaan LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, 2, B-1050 Brussel (BE). KATHOLIEKE UNI¬ SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, VERSITEIT LEUVEN, K.U.LEUVEN R&D [BE/BE]; GW, ML, MR, NE, SN, TD, TG). Waaistraat 6 - bus 5105, B-3000 Leuven (BE). UNI¬ Published: VERSITEIT GENT [BE/BE]; Sint-Pietersnieuwstraat 25, B-9000 Gent (BE). — with international search report (Art. 21(3)) — before the expiration of the time limit for amending the (72) Inventors; and claims and to be republished in the event of receipt of (75) Inventors/ Applicants (for US only): SCHYMKOWITZ, amendments (Rule 48.2(h)) Joost [BE/BE]; Attenrodestraat 15, B-3391 Meensel- Kiezegem (BE). ROUSSEAU, Frederic [BE/BE]; Stichel- — with sequence listing part of description (Rule 5.2(a)) berg 18, B-1702 Groot-Bijgaarden (BE). (54) Title: MOLECULES AND METHODS FOR INHIBITION AND DETECTION OF PROTEINS (57) Abstract: The present application belongs to the field of functional peptides and more particularly to the field of controlled pro - tein aggregation. The invention discloses molecules of a peptide structure as defined in the claims and methods of using such mo - lecules for therapeutic applications and for diagnostic uses, as well as in other applications such as in the agbio field and in industrial biotechnology. The molecules can be used for curing and/or stabilizing infections such as bacterial,fungal and viral diseases, but are also useful in non-infectious human and veterinary diseases. The molecules can also be used for the detection of protein biomarkers and for the prognosis and diagnosis of a variety of diseases. Molecules and methods for inhibition and detection of proteins Field of the invention The present application belongs t o the field of functional peptides and more particularly to the field of controlled protein aggregation. The invention discloses molecules of a peptide structure as defined in the claims and methods of using such molecules for therapeutic applications and for diagnostic uses, as well as in other applications such as in the agbio field and in industrial biotechnology. The molecules can be used for curing and/or stabilizing infections such as bacterial, fungal and viral diseases, but are also useful in non-infectious human and veterinary diseases. The molecules can also be used for the detection of protein biomarkers and for the prognosis and diagnosis of a variety of diseases. Background Protein aggregation is caused by the misfolding and subsequent agglutination of proteins in insoluble agglomerates. Protein aggregation is essentially a self-association process in which many identical protein molecules form higher order conglomerates of low solubility that eventually precipitate. On the basis of their macroscopic morphology, they are generally classified as either ordered or disordered aggregates. Under physiological conditions, almost any protein can be induced at high concentration to form amorphous aggregates; under the same conditions, a much smaller set of proteins form highly ordered β-rich amyloid fibers. However, on a microscopic level, the differentiation between these two types of aggregates is more subtle. Amorphous aggregates are not just clusters of misfolded proteins that stick t o each other through non-specific hydrophobic contacts. Rather, they are also often enriched in cross-β structure and their formation propensity correlates not only with hydrophobicity, but also with secondary structure propensity and charge, suggesting a specific mechanism of formation (Chiti et al., PNAS 99:16419-16426 (2002); Chiti et al., Nature 424:805-808 (2003); Chiti et al., Nat Struct Biol 9:137-143 (2002)). On the other hand, not all reported aggregates and fibers are enriched in β-structure, as both amorphous aggregates and fibers have been reported that retain native-like spectral properties and even enzymatic activity. In these cases, aggregation is proposed to occur by other mechanisms of oligomerization, such as three-dimensional domain swapping (Rousseau et al., PNAS 98: 5596-5601, 2001; Liu and Eisenberg, Protein Sci 11: 1285-1299, 2002) as is often seen in protein dimers. The focus on protein aggregation is, for a large part, inspired by the observation that a range of human diseases are characterized by protein deposits composed of one or a very limited number of proteins. Examples of such diseases where conversion of normally soluble proteins into conformationally altered insoluble proteins is known to be of causal relevance are for example the occurrence of amyloid beta peptide in Alzheimer's disease and cerebral amyloid angiopathy, a-synuclein deposits in Lewy bodies of Parkinson's disease, prions in Creutzfeldt-Jacob disease, superoxide dismutase in amyotrophic lateral sclerosis and tau in neurofibrillary tangles in frontal temporal dementia and Pick's disease. Thus far, protein aggregation has mainly been studied as an unwanted, disease-causing phenomenon and it is now widely accepted that cross-beta mediated aggregation is the most frequently occurring and biologically relevant mechanism of aggregation. Although protein aggregation has long been considered to be a disordered process mediated by non-specific hydrophobic interactions, it is now clear that particularly amyloid aggregation is in many instances essentially a specific self-association process. Aggregates formed both in vitro and in vivo are generally enriched in one particular protein and although aggregation is a spontaneous process in vitro, in the cellular environment this process is actively controlled by chaperones. The most common mechanism by which misfolded proteins aggregate consists in the self-association of specific polypeptide segments from identical proteins into a growing intermolecular beta sheet (e.g. Makin et al., PNAS 102(2): 315-20 (2005); Sawaya et al., Nature 447(7143):453-7 (2007)). These aggregation-nucleating segments are generally short, consisting of 5-15 residues, and can be accurately predicted using available biophysical algorithms. There is now abundant data to show that the individual strands interact to form an intermolecular beta sheet and that this structure forms the backbone of the aggregate. Aggregating sequences are very common in globular proteins, and occur with about the same frequency in , β, +β and / β proteins (SCOP classification : Lo Conte et al., Nucleic Acids Res 28:257-259 (2000)) (Linding et al., J Mol Biol 342: 345- 353 (2004)). These short aggregation-prone stretches are sufficient t o induce aggregation of a protein, as shown by grafting experiments which demonstrated that transplanting an aggregation-nucleating segment from an aggregating protein on a non-aggregating one transfers both aggregation propensity and aggregate structure from the former t o the latter (Esteras-Chopo et al., PNAS 102: 16672-16677, 2005). It can be considered that aggregation-sensitive protein sequences are the price to be paid for the existence of globular protein structures: as tertiary sidechain interactions mainly occur in the hydrophobic core, protein stretches spanning this region generally have a propensity to aggregate. However, for native globular proteins, aggregation is generally not an issue, as aggregation-prone protein stretches are generally sequestered by the protein structure and thereby protected from self- association. On the other hand, during protein translation and folding, or in the case of cellular stress or destabilizing mutations, partially unfolded states are much more likely to self-associate and induce aggregation and amyloidosis. Since most proteins harbor aggregation-prone peptide sequences within their primary structure, and since aggregation is sequence specific, it was previously successfully shown that it was possible to develop a general strategy for the specific induction of aggregation of a chosen target protein (see WO2007071789).