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| OF THE INVENTION The glycerine derivatives of the invention are compounds of the formula ##STR3## ... |
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| I claim: 1. A pharmaceutical composition useful for photodynamic therapy which composition contains,... |
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| Amplifier molecules for enhancement of diagnosis and therapy |
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| Peptide-containing polyethylene glycol derivatives and application thereof |
| OF THE PREFERRED EMBODIMENTS The present invention will hereinafter be explained in more detail. T... |
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| Modified HIL-6 |
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| Construction of geometrical objects from polynucleotides |
| By means of the present invention, DNA, RNA and similar polymers may be produced by synthesizing a ... |
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| Starburst conjugates |
| In its broadest aspect, the present invention is directed to polymer conjugate materials comprising ... |
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Nucleic acid probes
| Details |
Inventors: Urdea, Michael S.; Horn, Thomas;
Assignee: Chiron Corporation (Emeryville, CA)
Primary Examiner: Kepplinger; Esther L.
Assistant Examiner: Spiegel; Carol A.
Attorney, Agent or Firm: Morrison & Foerster
Modified nucleotides are provided which have the structure ##STR1## wherein R.sup.1 is a reactive group derivatizable with a detectable label, R.sup.2 is an optional linking moiety including an amide, thioether or disulfide linkage or a combination thereof, R.sup.3 is hydrogen, methyl, bromine, fluorine or iodine, R.sup.4 is hydrogen, an acid-sensitive, base-stable blocking group of an acyl capping group, R.sup.5 is hydrogen or a phosphorus derivative, R.sup.6 is H, OH, or OR where R is a protecting group and x is an integer in the range of 1 and 8 inclusive. Methods of synthesizing the derivatizable nucleotide are disclosed, as are labeled polynucleotide probes prepared therefrom. |
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DETAILED DESCRIPTION OF THE INVENTION "Derivatizable" nucleotides are nucleotides modified so as to include at the 4-position of a pyrimidine a functional group which can react with a detectable label.
An example of a derivatizable nucleotide is one which has been modified at the 4-position with an alkylamine moiety so that a free amine group is present on the structure.
"Derivatized" nucleotides are nucleotides in which the derivatizable functional group at the 4-position of the pyrimidine is bound, covalently or otherwise, directly or indirectly, to a detectable label.
"Alkylamine nucleotides" are nucleotides having an alkylamine group at the 4-position of a pyrimidine, bound to the structure in such a way as to provide a free amine group at that position.
A "polynucleotide" is a nucleotide chain structure containing at least two nucleotides.
The "polynucleotide probe" provided herein is a nucleotide chain structure, as above, containing at least two nucleotides, at least one of which includes a modified nucleotide which has substantially the same structure as that given by Formula 1.
"Detectable label" refers to a moiety which accounts for the detectability of a complex or reagent.
In general, the most common types of labels are fluorophores, chromophores, radioactive isotopes, and enzymes.
"Fluorophore" refers to a substance or portion thereof which is capable of exhibiting fluorescence in the detectable range.
Typically, this fluorescence is in the visible region, and there are common techniques for its quantitation.
Examples of fluorophores which are commonly used include fluorescein (usually supplied as fluorescein isothiocyanate [FITC] or fluorescein amine), rhodamine, dansyl and umbelliferone.
The nucleotide numbering scheme used herein is illustrated by Formulae 2-5.
##STR3## In a preferred embodiment, the substituents of the modified nucleotide of Formula 1 are as follows.
R.
sup.
1, which is a reactive group derivatizable with a detectable label, is preferably --NH.
sub.
2, --COOH or --SH
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