Two people were killed in clashes that broke out between pro-Moscow and pro-Kiev supporters in Ukraine's Russian-speaking city of Kharkiv, police said on Saturday, the second such deadly incident in as many days in the country's tinderbox east.

One pro-Russia protester and a passerby were killed when Ukrainian nationalists opened fire on a group of men trying to storm their headquarters in the city late on Friday, police sources told Agence France Presse.

Ukraine braced Saturday for a highly-charged breakaway vote in Crimea which is likely to see the peninsula annexed by Russia despite the threat of stiff sanctions, and push East-West tensions to breaking point.

An eleventh-hour diplomatic push by the United States to stop the referendum from going ahead failed on Friday, with Moscow refusing to make any decisions until after Crimea votes on a split from Ukraine on Sunday.

Since his return to the Kremlin, Vladimir Putin has grown more powerful than ever before. The strongman, who has ruled Russia for the past 14 years, has muzzled his opponents, check-mated the West on Syria and is now on the verge of annexing Crimea.

On Friday, the Kremlin upped the ante further, hinting it could move forces beyond Ukraine's peninsula to protect his compatriots.

The United States expressed revulsion Friday at the prospect of Syrian President Bashar Assad running for re-election, three years into a crushing civil war triggered by an uprising against his family's lengthy rule.

"We've been clear that Assad has lost all legitimacy to lead his people and any sort of campaign that he might run would be offensive and disgusting, I think, after what he's done to his people over the last many, many months," State Department deputy spokeswoman Marie Harf said.

A United States surveillance drone has been intercepted above the Ukrainian region of Crimea, a Russian state arms and technology group said Friday.

"The drone was flying at about 4,000 meters (12,000 feet) and was virtually invisible from the ground. It was possible to break the link with U.S. operators with complex radio-electronic" technology, said Rostec in a statement.

The United States and Russia failed on Friday to resolve a Cold-War-style crisis sparked by Moscow's military intervention in Crimea and the Ukrainian peninsula's weekend referendum on joining Kremlin rule.

U.S. Secretary of State John Kerry met his Russian counterpart Sergei Lavrov in London with few hopes that Sunday's Moscow-backed referendum in the strategic Black Sea peninsula that has been seized by Kremlin troops could be averted or delayed.

Russia has launched a criminal investigation into Ukrainian nationalist leader Oleg Tyagnybok for allegedly fighting Russian forces in Chechnya, the powerful Investigative Committee said Friday, in a largely symbolic move.

Tyagnybok, the leader of the parliamentary faction of the Svoboda (Freedom) party, is suspected of fighting "on the side of Chechen separatists from 1994 to 1995," the Investigative Committee said in a statement.

Around 500 Crimean Tatars took to the streets after prayers on Islam's holy day Friday to protest against an "illegal" referendum on closer ties with Russia which they plan to boycott.

Waving Ukrainian flags and chanting "Go away Putin" and "Russian soldiers go home", the protestors lined one of the main roads in Bakhchysaray, the biggest Tatar settlement in Crimea.

The pro-Moscow leader of Ukraine's flashpoint Crimea peninsula called Friday on Russian-speaking eastern regions of Ukraine to hold their own referendums on switching over to Kremlin rule.

"If a sufficient number of people support it in those regions, then they should also have referendums," self-declared prime minister Sergiy Aksyonov told reporters ahead of Sunday's referendum in Crimea, which has been backed by Moscow but denounced as illegal by Kiev and much of the international community.

Russia on Friday declared it reserved the right to protect compatriots in the whole of Ukraine, seen as a threat that Moscow could move its forces beyond the Russian-speaking peninsula of Crimea.

The Kremlin's latest statement comes after a protester was killed in clashes in the east of the ex-Soviet country on Thursday, and as Russian Foreign Minister Sergei Lavrov and U.S. Secretary of State John Kerry hold talks on the Ukraine crisis in London.