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WO1996010176A1 - Moyen d'inactivation reversible de molecules biologiques - Google Patents

Moyen d'inactivation reversible de molecules biologiques Download PDF

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Publication number
WO1996010176A1
WO1996010176A1 PCT/US1995/012310 US9512310W WO9610176A1 WO 1996010176 A1 WO1996010176 A1 WO 1996010176A1 US 9512310 W US9512310 W US 9512310W WO 9610176 A1 WO9610176 A1 WO 9610176A1
Authority
WO
WIPO (PCT)
Prior art keywords
target
molecular
reagent
binding
affinity
Prior art date
Application number
PCT/US1995/012310
Other languages
English (en)
Inventor
Thomas Reichert
Original Assignee
Becton Dickinson And Company
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Becton Dickinson And Company filed Critical Becton Dickinson And Company
Publication of WO1996010176A1 publication Critical patent/WO1996010176A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
    • C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
    • C07K1/1077—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
    • C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
    • C07K1/1075—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of amino acids or peptide residues
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • binding molecules having specific affinity foi a particular moleculai species is a well-known technique in both the diagnostic and therapeutic fields
  • the binding molecule generally an antigen or antibody specific foi its target is ordinarily selected for its ability to bind tightly to its target
  • binding molecules are not a viable option in most situations, since it is desirable, and peihaps even necessary, to keep the binding molecule taiget complexes intact until leveisal is des ⁇ ed
  • Lowei affinity binding molecules will become oie easily dissociated fiom the taiget, thereby pioducing a i educed effect with attendant loss of sensitivity and usually also, specificity
  • the instant invention presents a means whereby the activity of a biomolecular substance may be temporarily suspended and subsequently reactivated when desired
  • the invention involves the creating of a complex oi compound reagent, which is formed by linking together a plurality of molecular binding segments which, each individually, express a low or moderate affinity for a particular taiget species
  • a complex oi compound reagent which is formed by linking together a plurality of molecular binding segments which, each individually, express a low or moderate affinity for a particular taiget species
  • Such compound reagents possess a much greater affinity for the taiget than the meie sum of the low affinities for the target of each of the molecular binding segments and, indeed, if the compound reagents could be constructed such that each molecular binding segment would act independently of the others, the affinity of the compound reagent would be the product of the individual affinities. Further, because the binding occurs at multiple sites, the "off-time" will be quite long.
  • molecular binding segments are connected or linked together by molecular S95/12310
  • a wide array of applications can benefit from the use of this invention, expressed as a target molecule, which can be reversibly bound to a compound reagent. If the reagent exerts an inhibitory effect on the activity of the target, the target can be inhibited until desired, and then "switched on” by lysing the linkers. Alternatively, if the reagent exerts a catalytic or positive effect on the target molecule, the lysis can be utilized to "switch off the activity. This permits significant latitude in the ultimate end use.
  • the compound reagent will have an affinity greatei than any of the low affinity reagent substituents, in general, much greatei Because of the multipartite binding the "off-time" of such a leagent should inciease even moie than the proportionate inciease m affinity
  • the compound reagent will usually be "constructed” so that it will have a compound affinity at least as gieat as a very high affinity antibody, with an "off time of hours to days
  • the specificity will, by virtue of the requirement for binding of the multiple low affinity reagents, simultaneously, be very great, thus, one oi more of the low affinitv reagents may have a level of specificity for the target less than would be toleiable in a single reagent
  • the low affinity reagent segments can be any linkable elements, which exhibit both binding affinity for the target combined with the desired degree of specificity
  • linkable elements include antibodies, haptens. nucleic acids, certain carbohydrates, and certain protems
  • linkage segments are useful, since the pynmidine-specific endonucleases piesent in human serum will be ineffective in lysing such linkers Such linkage segments would, howevei, be quite susceptible to pu ⁇ ne-specific endonucleases from bacterial species Divalent zinc is known to slowly degrade RNA at physiological pH, and thus might be a candidate for effectuating time release, m vivo.
  • a specific application is anti-coagulation of blood by the specific inhibition of thrombin, with the selective option of disrupting other enzyme systems, and with the additional option of reversing any inhibition emplaced, without disrupting chemical environments necessary for physiological function, e.g., divalent ion dependent chemistiy
  • iNCEs reagents which have some activity, but insufficient specificity and/or affinity
  • a compound specie, comprised of the iNCEs which bind to different sites linked together will, in general, have an affinity higher than any of its components.
  • the specificity of the compound iNCE will be much greater than that of any component iNCE.
  • the links for a compound iNCE can be constructed of at least two types of linker units, one resistant to ambient degradative effects (e.g. endonucleases), and one sensitive thereto, then the compound iNCE could be synthesized to be completely resistant to degradation, completely sensitive to degradation, and

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biochemistry (AREA)
  • Analytical Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

Cette invention se rapporte à des réactifs complexes ou composés de haute affinité constitués d'une pluralité d'espèces présentant une affinité faible à modérée vis-à-vis d'une cible donnée, et reliés par des segments de liaison pouvant être facilement rompus ou lysés. Une fois lysées, les espèces individuelles présentent une affinité réduite pour la cible, et sont ainsi liées de manière réversible.
PCT/US1995/012310 1994-09-28 1995-09-26 Moyen d'inactivation reversible de molecules biologiques WO1996010176A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US31455194A 1994-09-28 1994-09-28
US08/314,551 1994-09-28

Publications (1)

Publication Number Publication Date
WO1996010176A1 true WO1996010176A1 (fr) 1996-04-04

Family

ID=23220402

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1995/012310 WO1996010176A1 (fr) 1994-09-28 1995-09-26 Moyen d'inactivation reversible de molecules biologiques

Country Status (1)

Country Link
WO (1) WO1996010176A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996035779A3 (fr) * 1995-05-09 1997-02-13 Dynal As Procede pour activer une enzyme immobilisee et inactivee d'une maniere reversible, par liberation d'un support d'immobilisation et son utilisation dans des reactions d'amplification d'acides nucleiques
US7056669B2 (en) 1996-11-05 2006-06-06 Clinical Micro Sensors, Inc. AC methods for the detection of nucleic acids

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5270163A (en) * 1990-06-11 1993-12-14 University Research Corporation Methods for identifying nucleic acid ligands

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5270163A (en) * 1990-06-11 1993-12-14 University Research Corporation Methods for identifying nucleic acid ligands

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996035779A3 (fr) * 1995-05-09 1997-02-13 Dynal As Procede pour activer une enzyme immobilisee et inactivee d'une maniere reversible, par liberation d'un support d'immobilisation et son utilisation dans des reactions d'amplification d'acides nucleiques
US7056669B2 (en) 1996-11-05 2006-06-06 Clinical Micro Sensors, Inc. AC methods for the detection of nucleic acids

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